Tricyclic compound

ABSTRACT

The present invention provides a compound of the formula (I): 
     
       
         
         
             
             
         
       
     
       
     wherein A ring, B ring and C ring are each independently optionally substituted aromatic carbocycle or optionally substituted 5- or 6-membered heterocycle which may fuse with benzene ring, 
     W 1 , W 2  and/or W 3  represents a bond when A ring, B ring and/or C ring is optionally substituted 5-membered heterocycle, 
     X is —O—, —NR 1 — wherein R 1  is hydrogen, lower alkyl etc. or the like, 
     Y is hydrogen, lower alkyl, lower alkenyl or the like, 
     one of V 1  and V 2  is a bond, and the other is a bond, —O— or the like, 
     and a pharmaceutical composition comprising the same.

This application is the national phase under 35 U.S.C. §371 of PCTInternational Application No. PCT/JP99/00297 which has an Internationalfiling date of Jan. 26, 1999, which designated the United States ofAmerica.

TECHNICAL FIELD

The present invention relates to a novel tricyclic compound and apharmaceutical composition for use as an immunosuppressant, ananti-allergic agent or a suppressant of the IgE production comprisingthe same.

BACKGROUND ART

A serious problem of a transplantation of a tissue or an organ which isfrequently performed in recent years is a rejection symptom forexcluding a transplanted part after an operation. Prevention of therejection symptom is very important for a success of thetransplantation.

Various immunosuppressants such as azathioprine, corticoid, CyclosporinA, Tacrolimus and the like are developed and come into practical use forprevention and a treatment of a rejection symptom against atransplantation of an organ or a tissue or a graft-versus-host reactionwhich is caused by a bone marrow transplantation. But they are not sosatisfactory in view of their effects and side effects.

Allergic diseases such as atopic dermatitis, allergic rhinitis,bronchial asthma, allergic conjunctivitis and the like tend to globallyincrease in recent years and become serious problems. The conventionalantiinflammatory agents are suppressants of releasing chemical mediatorsfrom mast cells, receptor inhibitors of the released chemical mediators,suppressants of allergic inflammation response or the like. All of theseare agents for symptomatic therapy and are not fundamental therapeuticagents for allergic diseases.

Therefore, the development of a more effective and safer medicinal agenthas been expected.

The compounds having a similar structure to a compound of the presentinvention and exhibiting an immunosuppressive or anti-allergic effectare described in WO94/27980, WO95/13067, WO96/40659, WO96/40143,WO96/38412, WO97/24356, WO97/24324, WO97/46524, JP-A 8-3163, JP-A9-12457, JP-A 9-71564, JP-A 9-124571 and the like. The liquid crystalcompounds are described in JP-A 9-87253, JP-A 63-253065, JP-A 1-106864,JP-A 1-106871, JP-A 2-83346, JP-A 9-48760, JP-A 9-31063 and the like,the compounds exhibiting an insecticide or acaricide activity aredescribed in JP-A 8-193067 and the compounds having a therapeuticactivity for circulatory system or psychopathy diseases are described inEP0600717 A1, all of which have a similar structure to a compound of thepresent invention.

DISCLOSURE OF THE INVENTION

The present invention provides a compound of the formula (I):

 

wherein A ring, B ring and C ring are each independently optionallysubstituted aromatic carbocycle or optionally substituted 5- or6-membered heterocycle which may fuse with benzene ring,

W¹, W² and/or W³ represents a bond when A ring, B ring and/or C ring isoptionally substituted 5-membered heterocycle,

X is —O—, —CH₂—, —NR¹— wherein R¹ is hydrogen, optionally substitutedlower alkyl, lower alkenyl, lower alkylcarbonyl or optionallysubstituted lower alkoxycarbonyl or —S(O)p— wherein p is an integer of 0to 2,

Y is hydrogen, optionally substituted lower alkyl, optionallysubstituted lower alkenyl, optionally substituted lower alkynyl,optionally substituted acyl, optionally substituted cycloalkyl,optionally substituted cycloalkenyl, optionally substituted loweralkoxycarbonyl, optionally substituted sulfamoyl, optionally substitutedamino, optionally substituted aryl or optionally substituted 5- or6-membered heterocycle,

Y may be optionally substituted lower alkoxy when X is —CH₂—,

Y may be optionally substituted lower alkoxycarbonyl; optionallysubstituted lower alkylsulfonyl or optionally substituted arylsulfonylwhen X is —O— or —NR¹—, one of V¹ and V² is a bond and the other is abond, —O—, —NH—, —OCH₂—, —CH₂O—, —CH═CH—, —C≡—C—, —CH(OR²)— wherein R²is hydrogen or lower alkyl, —CO— or —NHCHR³— wherein R³ is hydrogen orhydroxy, and

at least one of A ring, B ring and C ring is optionally substitutedaromatic carbocycle and at least another one is optionally substituted5- or 6-membered heterocycle which may fuse with benzene ring when bothof V¹ and V² are single bonds,

pharmaceutically acceptable salt or hydrate thereof

The present invention provides a pharmaceutical composition for use asan immunosuppressant, an anti-allergic agent or a suppressant of the IgEproduction comprising the compound (I), pharmaceutically acceptable saltor hydrate thereof.

In one of the other embodiments, the present invention provides a methodfor suppressing an immune response or a method for treating and/orpreventing allergic diseases comprising administering the compound (I).In another embodiment, the present invention provides use of thecompound (I) for manufacturing a medicament for suppressing an immuneresponse or treating and/or preventing allergic diseases.

In the present specification, the term “halogen” includes fluorine,chlorine, bromine and iodine. Fluorine or chlorine is preferable.

The term “lower alkyl” includes straight or branched chain alkyl having1 to 10 carbon atoms, preferably 1 to 8 carbon atoms, more preferably 1to 6 carbon atoms, and most preferably 1 to 3 carbon atoms. For example,included are methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl,sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, hexyl, isohexyl,n-heptyl, isoheptyl, n-octyl, isooctyl, n-nonyl, n-decyl and the like.

As substituents of “optionally substituted lower alkyl”, exemplified arehalogen; hydroxy; lower alkoxy optionally substituted with lower alkoxy;acyl; acyloxy; carboxy; lower alkoxycarbonyl; mercapt; lower alkylthio;amino optionally substituted with hydroxy, lower alkyl or optionallysubstituted acyl; imino optionally substituted with hydroxy, loweralkoxy, carboxy(lower)alkoxy, aryl(lower)alkoxy or 5- or 6-memberedheterocycle; hydrazono optionally substituted with carbamoyl or loweralkoxycarbonyl; carbamoyl optionally substituted with lower alkyl oramino; thiocarbamoyl optionally substituted with lower alkyl; cycloalkyloptionally substituted with lower alkyl or lower alkoxy; cycloalkenyloptionally substituted with lower alkyl; cyano; phenyl optionallysubstituted with at least one substituent selected from the group ofhydroxy, lower alkyl, carboxy, lower alkoxycarbonyl and lower alkoxy; 5-or 6-membered heterocycle which may be substituted with lower alkyl andmay fuse with benzene ring; and the like. The lower alkyl may besubstituted with one or more of these substituents at any possiblepositions. Halogen; hydroxy; acyloxy; phenyl optionally substituted withlower alkyl or lower alkoxy; pyridyl or the like is preferable.

The part of lower alkyl in “lower alkoxy” is the same as the above“lower alkyl”.

As substituents for “optionally substituted lower alkoxy”, exemplifiedare halogen; hydroxy; lower alkoxy optionally substituted with acyloxy;acyl; acyloxy optionally substituted with hydroxy or carboxy; carboxy;lower alkoxycarbonyl; lower alkylthio; amino optionally substituted withlower alkyl; phenyl optionally substituted with lower alkyl or loweralkoxy; heterocycle; heterocyclylcarbonyloxy and the like.

The parts of lower alkyl in “lower alkoxycarbonyl”, “loweralkylsulfonyl”, “lower alkylsulfonyloxy”, “lower alkylthio”, “loweralkylamino” and “lower alkylenedioxy” are the same as the above “loweralkyl”. Substituents for “optionally substituted lower alkoxycarbonyl”,“optionally substituted lower alkylsulfonyl” and “optionally substitutedlower alkylthio” are the same as those for the above “optionallysubstituted lower alkoxy”.

The term “lower alkenyl” includes straight or branched chain alkenyl of2 to 10 carbon atoms, preferably 2 to 8 carbon atoms more preferably 3to 6 carbon atoms having at least one double bond at any possiblepositions. For example, included are vinyl, propenyl such as 2-propenyland the like, isopropenyl, butenyl, isobutenyl, prenyl, butadienyl,pentenyl, isopentenyl, pentadienyl, hexenyl, isohexenyl, hexadienyl,heptenyl, octenyl, nonenyl, decenyl and the like. Substituents for“optionally substituted lower alkenyl” are the same as those for theabove “optionally substituted lower alkoxy” and alkenyl substituted withhalogen or unsubstituted alkenyl is preferable.

The parts of lower alkenyl in “lower alkenyloxy”, “loweralkenyloxycarbonyl” and “lower alkenylamino” are the same as the above“lower alkenyl”. Substituents for “optionally substituted loweralkenyloxy”, “optionally substituted lower alkenyloxycarbonyl” and“optionally substituted lower alkenylthio” are the same as those for theabove “optionally substituted lower alkoxy”.

The term “lower alkynyl” includes straight or branched chain alkynylhaving 2 to 10 carbon atoms, preferably 2 to 8 carbon atoms, and morepreferably 3 to 6 carbon atoms and is exemplified by ethynyl, propynylsuch as 2-propynyl, butynyl such as 2-butynyl, pentynyl, hexynyl,heptynyl, octynyl, nonynyl, decynyl and the like. These have at leastone triple bond and may have some double bonds at any possiblepositions. Substituents for “optionally substituted lower alkynyl” arethe same as those for the above “optionally substituted lower alkoxy”.

The term “acyl” includes straight or branched chain aliphatic acylhaving 1 to 20 carbon atoms, preferably 1 to 15 carbon atoms, morepreferably 1 to 8 carbon atoms, more preferably 1 to 6 carbon atoms,most preferably 1 to 4 carbon atoms, cyclic aliphatic acyl having 4 to 9carbon atoms, preferably 4 to 7 carbon atoms and aroyl. For example,formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl, pivaloyl,hexanoyl, acryloyl, propioloyl, methacryloyl, crotonoyl,cyclopropylcarbonyl, cyclohexylcarbonyl, cyclooctylcarbonyl, benzoyl andthe like are included. Substituents for “optionally substituted acyl”are the same as those for the above “optionally substituted loweralkoxy” and aroyl may further be substituted with lower alkyl. Among thesubstituents, halogen is preferable.

The part of acyl in “acyloxy” is the same as the above “acyl” andsubstituents for “optionally substituted acyloxy” are the same as thosefor the above “optionally substituted acyl”.

The term “lower alkylcarbonyl” includes aliphatic acyl having 2 to 4carbon atoms and included are acetyl, propyl, butyryl, isobutyryl andthe like. Acetyl is preferable.

The term “cycloalkyl” includes carbocycle having 3 to 6 carbon atoms andcyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like. Assubstituents for “optionally substituted cycloalkyl” exemplified arelower alkyl, halogen, hydroxy, carboxy, lower alkoxycarbonyl, loweralkoxy, lower alkylenedioxy, imino optionally substituted with loweralkoxy, aryl, 5- or 6-membered heterocycle and the like and thecycloalkyl may be substituted at any possible positions.

The term “cycloalkenyl” includes the group having at least one doublebond at any possible positions in the above cycloalkyl and isexemplified by cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl,cyclohexadienyl and the like. Substituents for “optionally substitutedcycloalkenyl” are the same as those for the above “cycloalkyl”.

As substituents for “optionally substituted amino”, exemplified areoptionally substituted lower alkyl {wherein the substituents are loweralkoxy, cycloalkyl, optionally substituted amino (wherein thesubstituents are aroyl optionally substituted withacyloxy(lower)alkoxy), optionally substituted aryl (wherein thesubstituents are lower alkyl, lower alkoxy, carboxy or loweralkoxycarbonyl) or heterocycle}; lower alkenyl; lower alkynyl;cycloalkyl; aryl optionally substituted with lower alkyl, carboxy, acyl,lower alkoxycarbonyl; sulfamoyl optionally substituted with lower alkyl;optionally substituted lower alkoxycarbonyl (the substituents arehalogen, acyloxy, acyloxy substituted with hydroxy, acyloxy substitutedwith carboxy or heterocyclylcarbonyloxy or the like); loweralkylsulfonyl and the like.

The term “optionally substituted carbamoyl” includes carbamoyloptionally substituted with lower alkyl, lower alkenyl, lower alkynyl orthe like.

The term “optionally substituted sulfamoyl” includes sulfamoyloptionally substituted with lower alkyl, lower alkenyl, lower alkynyl orthe like.

The term “aromatic carbocycle” includes benzene ring, naphthalene ring,anthracene ring, phenanthrene ring, indene ring and the like and benzenering is preferable.

The term “aryl” includes phenyl, naphthyl, anthryl, phenanthryl, indenyland the like and phenyl is preferable.

As substituents for “optionally substituted aromatic carbocycle” and“optionally substituted aryl”, exemplified are halogen; hydroxy; loweralkyl optionally substituted with halogen or carboxy; lower alkoxyoptionally substituted with halogen, aryl, heteroaryl or lower alkoxy;lower alkenyl; lower alkynyl; cycloalkyl; lower alkenyloxy; loweralkynyloxy; cycloalkoxy; acyl; acyloxy; carboxy; lower alkoxycarbonyl;lower alkenyloxycarbonyl; lower alkylthio; lower alkynylthio; aminooptionally substituted with lower alkyl, cycloalkyl(lower)alkyl,heteroaryl(lower)alkyl, lower alkenyl, cycloalkyl, acyl optionallysubstituted with halogen, lower alkoxycarbonyl, or lower alkylsulfonyl;guanidino; nitro; lower alkylsulfonyl; dihydroxyborane; loweralkylsulfonyloxy optionally substituted with halogen; arylsulfonyl;arylsulfonyloxy; aryl; 5- or 6-membered heterocycle and the like. Thearomatic carbocycle and aryl may be substituted with these substituentsat one or more of any possible positions. Preferable examples arehalogen; hydroxy; lower alkyl optionally substituted with halogen; loweralkoxy optionally substituted with aryl or lower alkoxy; loweralkenyloxy; acyloxy; lower alkylthio; amino optionally substituted withlower alkyl, lower alkenyl, acyl optionally substituted with halogen, orlower alkylsulfonyl; nitro; lower alkylsulfonyl; lower alkylsulfonyloxyoptionally substituted with halogen; or arylsulfonyloxy.

The parts of aryl in “arylsulfonyl” and “arylsulfonyloxy” are the sameas the above “aryl” and phenyl is preferable. Substituents for“optionally substituted arylsulfonyl” are the same as those for theabove “optionally substituted aryl” and unsubstituted arylsulfonyl ispreferable.

The term “5- or 6-membered heterocycle” includes 5- or 6-memberedheterocycle which contains at least one of hetero atoms arbitrarilyselected from a group of O, S and N. Examples of heterocycle includearomatic heterocycle such as pyrrole ring, imidazole ring, pyrazolering, pyridine ring such as 4-pyridyl, pyridazine ring, pyrimidine ring,pyrazine ring, triazole ring, triazine ring, isoxazole ring, oxazolering, oxadiazole ring, isothiazole ring, thiazole ring, thiadiazolering, furan ring such as 2-furyl or 3-furyl, thiophene ring such as3-thienyl and the like, aliphatic heterocycle such as tetrahydropyranering, dihydropyridine ring such as 1,2-dihydropyridyl, dihydropyridazinesuch as 2,3-dihydropyridazinyl, dihydropyrazine ring such as1,2-dihydropyrazinyl, dioxane ring, oxathiorane ring, thiane ring,pyrrolidine ring, pyrroline ring, imidazolidine ring, imidazoline ring,pyrazolidine ring, pyrazoline ring, piperidine ring, piperazine ring,morpholine ring and the like.

The term “5- or 6-membered heterocycle which contains one or two heteroatoms” includes aromatic heterocycle such as pyrrole ring, imidazolering, pyrazole ring, pyridine ring, pyridazine ring, pyrimicline ring,pyrazine ring, isoxazole ring, oxazole ring, isothiazole ring, thiazolering, furan ring, thiophene ring or the like and aliphatic heterocyclesuch as dioxane ring, oxathiorane ring, thiane ring, dihydropyridinering, pyrrolidine ring, pyrroline ring, imidazolidine ring, imidazolinering, pyrazolidine ring, pyrazoline ring, piperidine ring, piperazinering, morpholine ring or the like among the above “5- or 6-memberedheterocycle”. Aromatic heterocycle is preferable.

As “5- or 6-membered ring which may fuse with benzene ring”, exemplifiedare indole ring, isoindole ring, benzimidazole ring, indazole ring,cinnoline ring, phthalazine ring, quinazoline ring, benzisoxazole ring,benzoxazole ring, benzoxadiazole ring, benzothiazole ring,benzisothiazole ring, benzofuran ring, benzothiophen ring, benzotriazolering, isobenzofuran ring, chromen ring, indoline ring, isoindoline ringand the like.

As substituents for “optionally substituted 5- or 6-memberedheterocycle” and “optionally substituted 5- or 6-membered heterocyclewhich may fuse with benzene ring” exemplified are halogen; hydroxy;lower alkyl optionally substituted with hydroxy or acyloxy; lower alkoxyoptionally substituted with halogen, aryl or 5- or 6-memberedheterocycle; lower alkenyl; lower alkenyloxy; lower alkynyl; loweralkynyloxy; acyloxy; carboxy; lower alkoxycarbonyl; mercapt; loweralkylthio; lower alkenylthio; amino which may be mono- or di-substitutedwith halogen, optionally substituted lower alkyl wherein thesubstituents are cycloalkyl or 5- or 6-membered heterocycle, acyloptionally substituted with halogen, lower alkenyl, cycloalkyl, or loweralkylsulfonyl; imino optionally substituted with lower alkylsulfonyl;nitro; lower alkylsulfonyl; aryl; 5- or 6-membered heterocycle; oxo;oxide and the like. These substituents may substitute at one or more ofany possible positions.

The substituents for “optionally substituted 5- or 6-memberedheterocycle which contains one or two of hetero atoms” are the same asthe above. 5- or 6-membered heterocycle substituted with lower alkyl orunsubstituted one is preferable.

The term “W¹, W² and/or W³ represents a bond when A ring, B ring and/orC ring is optionally substituted 5-membered heterocycle” means asfollows: W¹ represents a bond when A ring is optionally substituted5-membered heterocycle, resulting in the binding positions of V¹ and Xto A ring as shown below.

 

Each of W² and W³ represents a bond when B ring or C ring is 5-memberedheterocycle, resulting in the binding positions of V¹ and V² shownbelow.

 

Each of X, V¹ and V² may directly bind to a hetero atom constituting Aring, B ring or C ring.

The term “compound (I)” includes formable and pharmaceuticallyacceptable salts of each compound. As “the pharmaceutically acceptablesalt”, exemplified are salts with mineral acids such as hydrochloricacid, sulfuric acid, nitric acid, phosphoric acid, hydrofluoric acid,hydrobromic acid and the like; salts with organic acids such as formicacid, acetic acid, tartaric acid, lactic acid, citric acid, fumaricacid, maleic acid, succinic acid and the like; salts with organic basesuch as ammonium, trimethylammonium, triethylammonium and the like;salts with alkaline metals such as sodium, potassium and the like andsalts with alkaline earth metals such as calcium, magnesium and thelike.

The compound of the present invention includes hydrates and all ofstereoisomers, for example, atropisomers etc. thereof.

BEST MODE FOR CARRYING OUT THE INVENTION

All of the compounds (I) have an immunosuppressive effect, ananti-allergic effect and/or a suppressive effect on the IgE productionand the following compounds are specifically preferable.

In the formula (I),

1) a compound wherein A ring is optionally substituted benzene ring,

preferably A ring is optionally substituted benzene ring {wherein thesubstituents are halogen, hydroxy, lower alkyl, lower alkoxy, acyloxy,lower alkylsulfonyl, optionally substituted lower alkylsulfonyloxy(wherein the substituents are halogen) or arylsulfonyloxy},

more preferably A ring is optionally substituted benzene ring (whereinthe substituents are halogen, hydroxy, lower alkyl, lower alkoxy orlower alkylsulfonyloxy),

2) a compound wherein B ring is optionally substituted benzene ring,optionally substituted pyridine ring, optionally substituted pyrimidinering, optionally substituted pyridazine ring, optionally substitutedpyrazine ring, optionally substituted thiophene ring, optionallysubstituted furan ring, optionally substituted pyrazole ring oroptionally substituted oxazole ring,

preferably B ring is optionally substituted benzene ring (wherein thesubstituents are halogen, hydroxy, lower alkyl, lower alkoxy, loweralkenyloxy, lower alkylthio, cycloalkoxy, lower alkoxycarbonyl or loweralkylsulfonyloxy), optionally substituted pyridine ring (wherein thesubstituents are halogen, hydroxy, lower alkyl, lower alkoxy, loweralkylthio, lower alkenyl, amino, carboxy or lower alkoxycarbonyl),

optionally substituted pyrimidine ring {wherein the substituents arehalogen, optionally substituted lower alkyl (wherein the substituentsare hydroxy or acyloxy), lower alkoxy, lower alkylthio, optionallysubstituted amino (wherein the substituents are lower alkyl), carboxy orlower alkoxycarbonyl},

optionally substituted pyridazine ring (wherein the substituents arehalogen, hydroxy, lower alkyl, lower alkoxy, lower alkylthio, loweralkenyl, amino, carboxy, lower alkoxycarbonyl or oxide),

optionally substituted thiophene ring (wherein the substituents arelower alkyl), optionally substituted pyrazole ring {wherein thesubstituents are optionally substituted lower alkyl (wherein thesubstituents are hydroxy), lower alkoxy, carboxy or loweralkoxycarbonyl},

or optionally substituted oxazole ring (wherein the substituents arelower alkyl), more preferably B ring is optionally substituted benzenering (wherein the substituents are hydroxy, lower alkyl, lower alkoxy orlower alkylsulfonyloxy), optionally substituted pyridine ring whereinthe substituents are halogen or lower alkyl),

optionally substituted pyrimidine ring {wherein the substituents areoptionally substituted lower alkyl (wherein the substituents are hydroxyor acyloxy), lower alkoxy, lower alkylthio, optionally substituted amino(wherein the substituents are lower alkyl), carboxy or loweralkoxycarbonyl},

optionally substituted pyrazole ring {wherein the substituents areoptionally substituted lower alkyl(wherein the substituents arehydroxy), lower alkoxy, carboxy or lower alkoxycarbonyl},

3) a compound wherein C ring is optionally substituted benzene ring,optionally substituted pyridine ring, optionally substituted pyrimidinering, optionally substituted pyridazine ring, optionally substitutedpyrazine ring, optionally substituted isoxazole ring, optionallysubstituted pyrazole ring, optionally substituted benzothiazole ring,optionally substituted morpholine ring, optionally substitutedpiperazine ring, optionally substituted imidazole ring, optionallysubstituted triazole ring, optionally substituted dihydropyridine ring,optionally substituted dihydropyridazine ring or optionally substituteddihydropyrazine ring, preferably C ring is optionally substitutedbenzene ring {wherein the substituents are halogen, hydroxy, optionallysubstituted lower alkyl (wherein the substituents are halogen),optionally substituted lower alkoxy (wherein the substituents are arylor lower alkoxy), lower alkenyloxy, lower alkylthio, optionallysubstituted amino {wherein the substituents are lower alkyl, loweralkenyl, optionally substituted acyl (wherein the substituents arehalogen) or lower alkylsulfonyl], nitro, lower alkylsulfonyl or loweralkylsulfonyloxy},

optionally substituted pyridine ring, optionally substituted pyrimidinering, optionally substituted pyridazine ring, optionally substitutedpyrazine ring, optionally substituted isoxazole ring, optionallysubstituted pyrazole ring (wherein the substituents are halogen,hydroxy, optionally substituted lower alkyl (wherein the substituentsare hydroxy or acyloxy), optionally substituted lower alkoxy (whereinthe substituents are halogen, aryl or 5- or 6-membered heterocycle),lower alkenyl, lower alkenyloxy, lower alkynyl, lower alkynyloxy,acyloxy, carboxy, lower alkoxycarbonyl, mercapt, lower alkylthio, loweralkenylthio, optionally mono- or di-substituted amino {wherein thesubstituents are halogen, optionally substituted lower alkyl (whereinthe substituents are cycloalkyl or 5- or 6-membered heterocycle),optionally substituted acyl (wherein the substituents are halogen),lower alkenyl, cycloalkyl or lower alkylsulfonyl}, optionallysubstituted imino (wherein the substituents are lower alkylsulfonyl),nitro, lower alkylsulfonyl, aryl, 5- or 6-membered heterocycle, oxo oroxide},

benzothiazole ring,

optionally substituted dihydropyridine (wherein the substituents areoxo), optionally substituted dihydropyridazine ring (wherein thesubstituents are oxo), optionally substituted dihydropyrazine ring(wherein the substituents are oxo), more preferably C ring is optionallysubstituted benzene ring {wherein the substituents are halogen, hydroxy,optionally substituted lower alkyl (wherein the substituents arehalogen), optionally substituted lower alkoxy (wherein the substituentsare aryl), lower alkenyloxy, lower alkylthio, optionally mono- ordi-substituted amino {wherein the substituents are lower alkyl, loweralkenyl, optionally substituted acyl (wherein the substituents arehalogen) or lower alkylsulfonyl], nitro, lower alkylsulfonyl or loweralkylsulfonyloxy},

optionally substituted pyridine ring {wherein the substituents arehalogen, hydroxy, lower alkyl, lower alkenyl, lower alkynyl, optionallysubstituted lower alkoxy (wherein the substituents are halogen, aryl or5- or 6-membered heterocycle), lower alkenyloxy, lower alkynyloxy, loweralkylthio, lower alkenylthio, optionally substituted amino (wherein thesubstituents are lower alkyl, heterocyclyl(lower)alkyl, cycloalkylalkyl,lower alkenyl or cycloalkyl), lower alkylsulfonyl, 5- or 6-memberedheterocycle, nitro or oxo},

optionally substituted pyrimidine ring {wherein the substituents arehalogen, hydroxy, optionally substituted lower alkoxy (wherein thesubstituents are aryl), lower alkenyloxy, or optionally substitutedamino (wherein the substituents are lower alkyl or lower alkenyl)},

optionally substituted pyridazine ring {wherein the substituents arehalogen, optionally substituted lower alkoxy (wherein the substituentsare aryl), lower alkenyloxy, or optionally substituted amino (whereinthe substituents are lower alkyl, lower alkoxy or lower alkenyl)},

optionally substituted pyrazine ring {wherein the substituents arehalogen, optionally substituted lower alkoxy (wherein the substituentsare aryl), lower alkenyloxy or optionally substituted amino (wherein thesubstituents are lower alkenyl)},

4) a compound wherein X is —O— or —NR¹— (wherein R¹ is hydrogen, methylor prenyl), preferably X is —O—, —NH— or —NMe—,

more preferably X is —O— or —NH—,

5) a compound wherein Y is hydrogen, optionally substituted lower alkyl,optionally substituted lower alkenyl, lower alkylsulfonyl or optionallysubstituted acyl, preferably Y is optionally substituted lower alkyl,optionally substituted lower alkenyl, lower alkylsulfonyl or optionallysubstituted acyl,

more preferably Y is optionally substituted lower alkyl {wherein thesubstituents are 5- or 6-membered heterocycle, or optionally substitutedphenyl (wherein the substituents are lower alkyl or lower alkoxy)} oroptionally substituted lower alkenyl (wherein the substituents arehalogen),

most preferably Y is methyl, optionally substituted prenyl (wherein thesubstituents are halogen) or optionally substituted benzyl (wherein thesubstituents are lower alkyl or lower alkoxy),

6) a compound wherein X is —O— or —NH— and Y is optionally substitutedprenyl (wherein the substituents are halogen), or optionally substitutedbenzyl(wherein the substituents are lower alkyl or lower alkoxy), or Xis —NR¹ and Y is methyl, preferably —X—Y is —OCH₂CH═CMe₂, —OBn,—OCH₂C₆H₄-2-Me, —OCH₂C₆H₄-3-Me, —OCH₂C₆H₄-4-Me, —OCH₂C₆H₄-4-OMe, —NMe₂or —NHCH₂CH═CMe₂, more preferably —X—Y is —OCH₂CH═CMe₂, —OBn or —NMe₂,

7) a compound wherein one of V¹ and V² is a single bond and the other isa single bond, —O— or —NH—,

preferably V¹ is a single bond and V² is a single bond, —O— or —NH—,more preferably both of V¹ and V² are single bonds,

8) a compound wherein A ring is optionally substituted benzene ring,

B ring is optionally substituted benzene ring, optionally substitutedpyridine ring, optionally substituted pyrimidine ring, optionallysubstituted pyridazine ring, optionally substituted pyrazine ring,optionally substituted thiophene ring, optionally substituted furanring, optionally substituted pyrazole ring or optionally substitutedoxazole ring,

C ring is optionally substituted benzene ring, optionally substitutedpyridine ring, optionally substituted pyrimidine ring, optionallysubstituted pyridazine ring, optionally substituted pyrazine ring,optionally substituted isoxazole ring, optionally substituted pyrazolering, optionally substituted benzothiazole ring, optionally substitutedmorpholine ring, optionally substituted piperazine ring, optionallysubstituted imidazole ring or optionally substituted triazole ring,

X is —O— or —NR¹— wherein R¹ is hydrogen, methyl or prenyl,

Y is optionally substituted lower alkyl or optionally substituted loweralkenyl, and one of V¹ and V² is a single bond and the other is a singlebond, —O— or —NH—, preferably A ring is optionally substituted benzenering {wherein the substituents are halogen, hydroxy, lower alkoxy,acyloxy, lower alkylsulfonyl, optionally substituted loweralkylsulfonyloxy (wherein the substituents are halogen) orarylsulfonyloxy},

B ring is optionally substituted benzene ring (wherein the substituentsare halogen, hydroxy, lower alkyl, lower alkoxy, lower alkoxycarbonyl,lower alkenyloxy or lower alkylsulfonyloxy),

optionally substituted pyridine ring (wherein the substituents arehalogen or lower alkyl),

optionally substituted pyrimidine ring {wherein the substituents areoptionally substituted lower alkyl (wherein the substituents are hydroxyor acyloxy), lower alkoxy, lower alkylthio, optionally substituted amino(wherein the substituents are lower alkyl), carboxy or loweralkoxycarbonyl)},

optionally substituted pyridazine ring (wherein the substituents arelower alkyl or oxide),

optionally substituted thiophene ring (wherein the substituents arelower alkyl), optionally substituted pyrazole ring {wherein thesubstituents are optionally substituted lower alkyl (wherein thesubstituents are hydroxy), lower alkoxy, carboxy, or loweralkoxycarbonyl},

or optionally substituted oxazole ring (wherein the substituents arelower alkyl),

C ring is optionally substituted benzene ring {wherein the substituentsare halogen, hydroxy, optionally substituted lower alkyl (wherein thesubstituents are halogen), optionally substituted lower alkoxy (whereinthe substituents are aryl or lower alkoxy), lower alkenyloxy, loweralkylthio, optionally substituted amino {wherein the substituents arelower alkyl, lower alkenyl, optionally substituted acyl (wherein thesubstituents are halogen) or lower alkylsulfonyl}, nitro, loweralkylsulfonyl or lower alkylsulfonyloxy},

optionally substituted pyridine ring {wherein the substituents arehalogen, hydroxy, lower alkyl, lower alkenyl, lower alkynyl, optionallysubstituted lower alkoxy (wherein the substituents are halogen, aryl or5- or 6-membered heterocycle), lower alkenyloxy, lower alkynyloxy, loweralkylthio, lower alkenylthio, optionally substituted amino (wherein thesubstituents are lower alkyl, heterocyclyl(lower)alkyl, cycloalkylalkyl,lower alkenyl or cycloalkyl), lower alkylsulfonyl, 5- or 6-memberedheterocycle, nitro or oxo},

optionally substituted pyrimidine ring {wherein the substituents arehalogen, hydroxy, optionally substituted lower alkoxy (wherein thesubstituents are aryl), lower alkenyloxy or optionally substituted amino(wherein the substituents are lower alkyl or lower alkenyl)},

optionally substituted pyridazine ring {wherein the substituents arehalogen, optionally substituted lower alkoxy (wherein the substituentsare aryl), lower alkenyloxy or optionally substituted amino (wherein thesubstituents are lower alkyl, lower alkoxy or lower alkenyl)},

optionally substituted pyrazine ring {the substituents are halogen,optionally substituted lower alkoxy (wherein the substituents are aryl),lower alkenyloxy, optionally substituted amino (wherein the substituentsare lower alkenyl)},

optionally substituted isoxazole ring {wherein the substituents areoptionally substituted lower alkoxy (wherein the substituents are aryl),lower alkenyloxy, or optionally substituted amino (wherein thesubstituents are lower alkenyl or lower alkylsulfonyl)},

optionally substituted pyrazole ring {wherein the substituents are loweralkyl, optionally substituted lower alkoxy (wherein the substituents arearyl), lower alkenyloxy, or optionally substituted amino (wherein thesubstituents are lower alkenyl or lower alkylsulfonyl)},

or benzothiazole ring,

X is —O—, —NH— or —NMe—,

Y is optionally substituted lower alkyl {wherein the substituents are 5-or 6-membered heterocycle or optionally substituted phenyl (wherein thesubstituents are lower alkyl or lower alkoxy)} or lower alkenyl (whereinthe substituents are halogen), and one of V¹ and V² is a single bond andthe other is a single bond, —O— or —NH—, more preferably A ring isoptionally substituted benzene ring (wherein the substituents arehalogen, hydroxy, lower alkoxy or lower alkylsulfonyloxy),

B ring is benzene ring (wherein the substituents are halogen, hydroxy,lower alkyl, lower alkoxy or lower alkoxycarbonyl),

optionally substituted pyridine ring (wherein the substituents arehalogen or lower alkyl),

optionally substituted pyrimidine ring {wherein the substituents areoptionally substituted lower alkyl (wherein the substituents are hydroxyor acyloxy), lower alkoxy, lower alkylthio, optionally substituted amino(wherein the substituents are lower alkyl), carboxy or loweralkoxycarbonyl},

optionally substituted pyrazole ring {wherein the substituents areoptionally substituted lower alkyl (wherein the substituents arehydroxy), lower alkoxy, carboxy, or lower alkoxycarbonyl},

C ring is optionally substituted benzene ring {wherein the substituentsare halogen, hydroxy, optionally substituted lower alkyl (wherein thesubstituents are halogen), optionally substituted lower alkoxy (whereinthe substituents are aryl), lower alkenyloxy, lower alkylthio,optionally substituted amino {wherein the substituents are lower alkyl,lower alkenyl, optionally substituted acyl (wherein the substituents arehalogen), or lower alkylsulfonyl}, nitro, lower alkylsulfonyl or loweralkylsulfonyloxy},

optionally substituted pyridine ring {wherein the substituents arehalogen, hydroxy, lower alkyl, lower alkenyl, lower alkynyl, optionallysubstituted lower alkoxy (wherein the substituents are halogen, aryl or5- or 6-membered heterocycle), lower alkenyloxy, lower alkynyloxy, loweralkylthio, lower alkenylthio, optionally substituted amino (wherein thesubstituents are lower alkyl, heterocyclyl(lower)alkyl, cycloalkylalkyl,lower alkenyl or cycloalkyl), lower alkylsulfonyl, 5- or 6-memberedheterocycle, nitro or oxo},

optionally substituted pyrimidine ring {wherein the substituents arehalogen, hydroxy, optionally substituted lower alkoxy (wherein thesubstituents are aryl), lower alkenyloxy or optionally substituted amino(wherein the substituents are lower alkyl or lower alkenyl)},

optionally substituted pyridazine ring {wherein the substituents arehalogen, optionally substituted lower alkoxy (wherein the substituentsare aryl), lower alkenyloxy or optionally substituted amino (wherein thesubstituents are lower alkyl, lower alkoxy or lower alkenyl)},

or optionally substituted pyrazine ring {wherein the substituents arehalogen, optionally substituted lower alkoxy (wherein the substituentsare aryl), lower alkenyloxy or optionally substituted amino (wherein thesubstituents are lower alkenyl)},

X is —O— and Y is prenyl or optionally substituted benzyl (wherein thesubstituents are lower alkyl or lower alkoxy) or X is —NR¹— and Y ismethyl.

V¹ is a single bond and V² is a single bond, —O— or —NH—, morepreferably A ring is optionally substituted benzene ring (wherein thesubstituents are halogen, hydroxy, lower alkoxy or loweralkylsulfonyloxy),

B ring is optionally substituted benzene ring (wherein the substituentsare halogen, hydroxy, lower alkyl, lower alkoxy or loweralkoxycarbonyl), optionally substituted pyridine ring (wherein thesubstituents are lower alkyl),

optionally substituted pyrimidine ring (wherein the substituents arelower alkyl, lower alkoxy, carboxy or lower alkoxycarbonyl),

optionally substituted pyrazole ring (wherein the substituents are loweralkyl, lower alkoxy, carboxy or lower alkoxycarbonyl),

C ring is optionally substituted benzene ring {wherein the substituentsare halogen, hydroxy, lower alkoxy, lower alkenyloxy, optionallysubstituted amino (wherein the substituents are lower alkyl) or loweralkylsulfonyloxy},

optionally substituted pyridine ring {wherein the substituents areoptionally substituted amino {wherein the substituents are halogen,lower alkyl, optionally substituted lower alkoxy (wherein thesubstituents are aryl or 5- or 6-membered heterocycle), lower alkenyloxyor optionally substituted amino (wherein the substituents are loweralkyl, heterocyclyl(lower)alkyl or lower alkenyl)},

optionally substituted pyrimidine ring (wherein the substituents arehalogen, hydroxy, lower alkoxy, lower alkenyloxy, amino or loweralkenylamino), optionally substituted pyridazine ring (wherein thesubstituents are halogen, lower alkoxy, lower alkenyloxy, amino, loweralkylamino or lower alkenylamino), or optionally substituted pyrazinering (wherein the substituents are lower alkenyloxy, amino or loweralkenylamino),

X is —O— and Y is prenyl or optionally substituted benzyl (wherein thesubstituents are lower alkyl or lower alkoxy) or X is NR¹ and Y ismethyl or prenyl,

V¹ is a single bond and V² is a single bond, —O— or —NH,

9) a compound wherein two of A ring, B ring and C ring are optionallysubstituted benzene ring and the other one is optionally substituted 5-or 6-membered heterocycle which may fuse with benzene ring,

preferably A ring is optionally substituted benzene ring, one of B ringand C ring is optionally substituted benzene ring and the other isoptionally substituted 5- or 6-membered heterocycle which may fuse withbenzene ring,

more preferably A ring is optionally substituted benzene ring, one of Bring and C ring is optionally substituted benzene ring and the other isoptionally substituted 5- or 6-membered heterocycle which may fuse withbenzene ring and both of V¹ and V² are single bonds,

10) a compound wherein all of A ring, B ring and C ring are optionallysubstituted benzene ring, V¹ is a single bond and V² is —O— or —NH—,

11) a compound wherein both of A ring and B ring are optionallysubstituted benzene ring and —X—Y is —NMe₂, prenyloxy or prenylamino,

preferably both of A ring and B ring are optionally substituted benzenering and C ring is optionally substituted pyridine ring, optionallysubstituted pyrimidine ring,

optionally substituted pyridazine ring, optionally substituted isoxazolering or optionally substituted pyrazole ring, —X—Y is —NMe₂, prenyloxyor prenylamino and both of V¹ and V² are single bonds,

12) a compound of any of following formulas

 

wherein R⁴, R⁵, R⁶ and R⁷ are each independently hydrogen, halogen,hydroxy, lower alkoxy, acyloxy, optionally substituted loweralkylsulfonyloxy (wherein the substituents are halogen) orarylsulfonyloxy,

R⁸, R⁹, R¹⁰ and R¹¹ are each independently hydrogen, hydroxy, loweralkyl, lower alkoxy or lower alkylsulfonyloxy,

R¹², R¹³, R¹⁴, R¹⁵ and R¹⁶ are each independently hydrogen, halogen,hydroxy, optionally substituted lower alkyl(wherein the substituents arehalogen), optionally substituted lower alkoxy (wherein the substituentsare aryl), lower alkenyloxy, lower alkylthio, lower alkylsulfonyl, loweralkylsulfonyloxy, nitro or optionally substituted amino {wherein thesubstituents are lower alkyl, lower alkenyl, optionally substituted acyl(wherein the substituents are halogen) or lower alkylsulfonyl},

B ring is optionally substituted pyridine ring (wherein the substituentsare halogen or lower alkyl),

optionally substituted pyrimidine ring {wherein the substituents areoptionally substituted lower alkyl (wherein the substituents are hydroxyor acyloxy), lower alkoxy, lower alkylthio, optionally substituted amino(wherein the substituents are lower alkyl), carboxy or loweralkoxycarbonyl},

optionally substituted pyridazine (wherein the substituents are loweralkyl or oxide), optionally substituted thiophene ring (wherein thesubstituents are lower alkyl),

optionally substituted pyrazole ring (wherein the substituents areoptionally substituted lower alkyl (wherein the substituents arehydroxy), lower alkoxy, carboxy or lower alkoxycarbonyl},

or optionally substituted oxazole ring (wherein the substituents arelower alkyl),

C ring is optionally substituted pyridine ring {wherein the substituentsare hydroxy, halogen, lower alkyl, optionally substituted lower alkoxy(wherein the substituents are aryl), lower alkenyloxy, optionallysubstituted amino (wherein the substituents are lower alkyl, optionallysubstituted acyl (wherein the substituents are halogen), lower alkenyl,or lower alkylsulfonyl}, nitro, lower alkylthio, lower alkylsulfonyl oroptionally substituted imino (wherein the substituents are loweralkylsulfonyl)},

optionally substituted pyrimidine ring {wherein the substituents arehalogen, hydroxy, optionally substituted lower alkoxy (wherein thesubstituents are aryl), lower alkenyloxy or optionally substituted amino(wherein the substituents are lower alkyl or lower alkenyl)},

optionally substituted pyridazine ring {wherein the substituents arehalogen, optionally substituted lower alkoxy (wherein the substituentsare aryl), lower alkenyloxy or optionally substituted amino (wherein thesubstituents are lower alkyl, lower alkoxy, lower alkenyl or loweralkenyloxy)},

optionally substituted pyrazine ring {wherein the substituents arehalogen, optionally substituted lower alkoxy (wherein the substituentsare aryl), lower alkenyloxy or optionally substituted amino (wherein thesubstituents are lower alkyl or lower alkenyl)},

optionally substituted isoxazole ring {wherein the substituents areoptionally substituted lower alkoxy (wherein the substituents are aryl),lower alkenyloxy or optionally substituted amino (wherein thesubstituents are lower alkenyl or lower alkylsulfonyl)},

optionally substituted pyrazole ring {wherein the substituents are loweralkyl, optionally substituted lower alkoxy (wherein the substituents arearyl), lower alkenyloxy or optionally substituted amino (wherein thesubstituents are lower alkenyl or lower alkylsulfonyl)},

benzothiazole ring,

morpholine ring,

piperazine ring (wherein the substituents are lower alkyl or phenyl),

imidazole ring or triazole ring,

V¹ is a single bond or —O—,

V² is a single bond, —O—, —NH—, —OCH₂—, —CH₂O—, —CH═CH—, —C≡—C—,—CH(OEt)—, —CH(OH)—, —CO—, —NHCH₂— or —NHCH(OH)—,

X is —O— or —NR¹— (wherein R¹ is hydrogen, optionally substituted loweralkyl, lower alkenyl, lower alkylcarbonyl or optionally substitutedlower alkoxycarbonyl), and Y is methyl, optionally substituted prenyl(wherein the substituents are halogen) or optionally substituted benzyl(wherein the substituents are lower alkyl or lower alkoxy)

13) a compound wherein both of A ring and B ring are optionallysubstituted benzene ring and C ring is

 

Y is CH₂CH═CMe₂ and both of V¹ and V² are single bonds,

14) a compound wherein both of A ring and B ring are benzene ring, Cring is

 

X is —O—, Y is hydrogen, and both of V¹ and V² are single bonds,

15) a compound wherein both of A ring and B ring is optionallysubstituted benzene ring, C ring is

 

X is —NH— and both of V¹ and V² are single bonds.

Another preferable embodiment is,

[1] a compound of the following formula (Ib′):

 

wherein C ring is optionally substituted 5- or 6-membered heterocyclewhich contains one or two hetero atoms and W³ represents a bond when Cring is 5-membered heterocycle,

X and X′ are each independently —O—, —CH₂—, —NR¹— wherein R¹ ishydrogen, optionally substituted lower alkyl, lower alkenyl, loweralkylcarbonyl or optionally substituted lower alkoxycarbonyl, or —S(O)p—wherein p is an integer of 0-2,

Y and Y′ are each independently optionally substituted lower alkyl,optionally substituted lower alkenyl, optionally substituted loweralkynyl, optionally substituted acyl, optionally substituted cycloalkyl,optionally substituted cycloalkenyl, optionally substituted loweralkoxycarbonyl, optionally substituted amino, optionally substitutedsulfamoyl, optionally substituted aryl or optionally substituted 5- or6-membered heterocycle,

R¹, taken together with Y or Y′, may form —(CH₂)m—, —(CH₂)₂—Q—(CH₂)₂—wherein Q is CH₂, O, S or NR′, —CR′═CH—CH═CR′—, —CH═N—CH═CH—,—N═CH—N═CH—, —C(═O)—O(CH₂)n—, —C(═O)—NR′—(CH₂)n— or —C(═O)—NR′—N═CH—wherein m is 4 or 5, n is 2 or 3,

R′ is hydrogen, lower alkyl or lower alkenyl,

Y may be optionally substituted lower alkoxy when X is —CH₂—, Y′ may beoptionally substituted lower alkoxy when X′ is —CH₂—,

Y may be optionally substituted lower alkoxycarbonyl, optionallysubstituted lower alkylsulfonyl or optionally substituted arylsulfonylwhen X is —O— or NR¹,

Y′ may be optionally substituted lower alkoxycarbonyl, optionallysubstituted lower alkylsulfonyl or optionally substituted arylsulfonylwhen X′ is —O— or —NR¹—,

Y may be hydrogen or halogen when X is —CH₂— or NR¹—,

Y′ may be hydrogen or halogen when X′ is —CH₂— or —NR¹—.

R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰ and R¹¹ are each independently hydrogen,halogen, hydroxy, optionally substituted lower alkyl, optionallysubstituted lower alkoxy, optionally substituted lower alkenyl,optionally substituted lower alkenyloxy, optionally substitutedcycloalkyloxy, optionally substituted acyloxy, carboxy, optionallysubstituted lower alkoxycarbonyl, optionally substituted loweralkenyloxycarbonyl, optionally substituted lower alkylthio, optionallysubstituted lower alkenylthio, optionally substituted amino, optionallysubstituted carbamoyl, guanidino, nitro, optionally substituted loweralkylsulfonyl, optionally substituted lower alkylsulfonyloxy, optionallysubstituted arylsulfonyl or optionally substituted arylsulfonyloxy,

excluding compounds wherein all of R⁸, R⁹, R¹⁰ and R¹¹ are selected fromhydrogen and halogen.

In the following compound of the formula (Ib′), preferable is:

a compound wherein R⁴ and R⁵ are each independently hydrogen, hydroxy,halogen, optionally substituted lower alkyl, optionally substitutedlower alkoxy, optionally substituted acyloxy, optionally substitutedlower alkylsulfonyloxy or optionally substituted arylsulfonyloxy(hereinafter referred to as “R⁴ and R⁵ are R45-1”),

a compound wherein R⁴ and R⁵ are each independently hydrogen, hydroxy,halogen, lower alkyl, lower alkoxy, acyloxy, optionally substitutedlower alkylsulfonyloxy or arylsulfonyloxy (hereinafter referred to as“R⁴ and R⁵ are R45-2”),

a compound wherein R⁴ and R⁵ are each independently hydrogen, halogen orlower alkoxy (hereinafter referred to as “R⁴ and R⁵ are R45-3”),

a compound wherein one of R⁴ and R⁵ is hydrogen and the other is halogen(hereinafter referred to as “R⁴ and R⁵ are R45-4”),

a compound wherein one of R⁴ and R⁵ is hydrogen and the other is chloroor fluoro (hereinafter referred to as “R⁴ and R⁵ are R45-5”),

a compound wherein R⁴ is hydrogen and R⁵ is halogen (hereinafterreferred to as “R⁴ and R⁵ are R45-6”),

a compound wherein R⁴ is hydrogen and R⁵ is chloro or fluoro(hereinafter referred to as “R⁴ and R⁵ are R45-7”),

a compound wherein R⁶ and R⁷ are each independently hydrogen, halogen orlower alkyl (hereinafter referred to as “R⁶ and R⁷ are R67-1”),

a compound wherein both of R⁶ and R⁷ are hydrogen (hereinafter referredto as “R⁶ and R⁷ are R67-2”),

a compound wherein R⁸ and R¹¹ are each independently hydrogen, halogen,hydroxy, optionally substituted lower alkyl, optionally substitutedlower alkoxy, optionally substituted cycloalkoxy, optionally substitutedlower alkylthio, optionally substituted lower alkoxycarbonyl oroptionally substituted lower alkylsulfonyloxy (hereinafter referred toas “R⁸ and R¹¹ are R811-1”),

compound wherein R⁸ and R¹¹ are each independently hydrogen, halogen,hydroxy, optionally substituted lower alkyl, optionally substitutedlower alkoxy, optionally substituted cycloalkoxy, optionally substitutedlower alkylthio, optionally substituted lower alkoxycarbonyl oroptionally substituted lower alkylsulfonyloxy (hereinafter referred toas “R⁸ and R¹¹ are R811-2”),

a compound wherein R⁸ and R¹¹ are each independently hydrogen, halogenhydroxy, optionally substituted lower alkyl, optionally substitutedlower alkoxy or optionally substituted lower alkoxycarbonyl (hereinafterreferred to as “R⁸ and R¹¹ are R811-3”),

a compound wherein R⁸ and R¹¹ are each independently hydrogen, halogen,optionally substituted lower alkyl, optionally substituted lower alkoxyor lower alkoxycarbonyl (hereinafter referred to as “R⁸ and R¹¹ areR811-4”),

a compound wherein R⁸ and R¹¹ are each independently hydrogen,optionally substituted lower alkyl, optionally substituted lower alkoxyor lower alkoxycarbonyl (hereinafter referred to as “R⁸ and R¹¹ areR811-5”),

a compound wherein R⁸ and R¹¹ are each independently hydrogen,optionally substituted lower alkyl or optionally substituted loweralkoxy (hereinafter referred to as “R⁸ and R¹¹ are R811-6”),

a compound wherein R⁸ and R¹¹ are each independently optionallysubstituted lower alkyl or optionally substituted lower alkoxy(hereinafter referred to as “R⁸ and R¹¹ are R811-7”),

a compound wherein R⁸ and R¹¹ are each independently lower alkyl orlower alkoxy (hereinafter referred to as “R⁸ and R¹¹ are R811-8”),

a compound wherein both of R⁸ and R¹¹ are optionally substituted loweralkyl or optionally substituted lower alkoxy (hereinafter referred to as“R⁸ and R¹¹ are R811-9”),

a compound wherein both of R⁸ and R¹¹ are lower alkyl, or one of R⁸ andR¹¹ is lower alkyl and the other is lower alkoxy (hereinafter referredto as “R⁸ and R¹¹ are R811-10”),

a compound wherein both of R⁸ and R¹¹ are lower alkyl (hereinafterreferred to as “R⁸ and R¹¹ are R811-11”),

a compound wherein R⁸ and R¹¹ are each independently methyl or methoxy(hereinafter referred to as “R⁸ and R¹¹ are R811-12”),

a compound wherein R⁹ and R¹⁰ are each independently hydrogen, halogen,hydroxy, optionally substituted lower alkyl, optionally substitutedlower alkoxy, optionally substituted cycloalkoxy, optionally substitutedlower alkylthio, optionally substituted lower alkoxycarbonyl oroptionally substituted lower alkylsulfonyloxy (hereinafter referred toas “R⁹ and R¹⁰ are R910-1”),

a compound wherein R⁹ and R¹⁰ are each independently hydrogen, halogen,hydroxy, optionally substituted lower alkyl, optionally substitutedlower alkoxy, cycloalkoxy, lower alkylthio, lower alkoxycarbonyl oroptionally substituted lower alkylsulfonyloxy (hereinafter referred toas “R⁹ and R¹⁰ are R910-2”),

a compound wherein R⁹ and R¹⁰ are each independently hydrogen, halogen,hydroxy, optionally substituted lower alkyl, optionally substitutedlower alkoxy or optionally substituted lower alkylsulfonyloxy(hereinafter referred to as “R⁹ and R¹⁰ are R910-3”),

a compound wherein R⁹ and R¹⁰ are each independently hydrogen, halogen,hydroxy, optionally substituted lower alkyl or optionally substitutedlower alkoxy (hereinafter referred to as “R⁹ and R¹⁰ are R910-4”),

a compound wherein R⁹ and R¹⁰ are each independently hydrogen,optionally substituted lower alkyl or optionally substituted loweralkoxy (hereinafter referred to as “R⁹ and R¹⁰ are R910-5”),

a compound wherein R⁹ and R¹⁰ are each independently hydrogen oroptionally substituted lower alkyl (hereinafter referred to as “R⁹ andR¹⁰ are R910-6”),

a compound wherein both of R⁹ and R¹⁰ are hydrogen or optionallysubstituted lower alkyl (hereinafter referred to as “R⁹ and R¹⁰ areR910-7”),

a compound wherein both of R⁹ and R¹⁰ are hydrogen or lower alkyl(hereinafter referred to as “R⁹ and R¹⁰ are R910-8”),

a compound wherein both of R⁹ and R¹⁰ are hydrogen (hereinafter referredto as “R⁹ and R¹⁰ are R910-9”),

a compound wherein both of R⁹ and R¹⁰ are lower alkyl (hereinafterreferred to as “R⁹ and R¹⁰ are R910-10”),

a compound wherein R⁹ and R¹⁰ are each independently hydrogen or loweralkyl (hereinafter referred to as “R⁹ and R¹⁰ are R910-11”),

a compound wherein C ring is 5- or 6-membered heterocycle which containsat least one N atom (hereinafter referred to as “C ring is C-1”),

a compound wherein C ring is a 6-membered heterocycle which contains atleast one N atom (hereinafter referred to as “C ring is C-2”),

a compound wherein C ring is optionally substituted pyridine, optionallysubstituted pyrimidine, optionally substituted pyridazine or optionallysubstituted pyrazine (hereinafter referred to as “C ring is C-3”),

a compound wherein C ring is optionally substituted pyridine oroptionally substituted pyrimidine (hereinafter referred to as “C ring isC-4”),

a compound wherein C ring is

 

 wherein G¹ is CR¹³ or N, G² is CR¹⁵ or N and R¹², R¹³, R¹⁴ and R¹⁵ areeach independently hydrogen, halogen, hydroxy, optionally substitutedlower alkyl, optionally substituted lower alkoxy optionally substitutedlower alkenyl, optionally substituted lower alkenyloxy, optionallysubstituted acyloxy, carboxy, optionally substituted loweralkoxycarbonyl, optionally substituted lower alkenyloxycarbonyl,optionally substituted lower alkylthio, optionally substituted loweralkenylthio, optionally substituted amino, guanidino, nitro, optionallysubstituted lower alkylsulfonyl, optionally substituted loweralkylsulfonyloxy, optionally substituted arylsulfonyl or optionallysubstituted arylsulfonyloxy (hereinafter referred to as “C ring isC-5”),

a compound wherein C ring is

 

 wherein G¹ is CR¹³ or N, G² is CR¹⁵ or N and R¹², R¹³, R¹⁴ and R¹⁵ areeach independently hydrogen, halogen, hydroxy, lower alkyl, optionallysubstituted lower alkenyl, optionally substituted lower alkoxy,optionally substituted amino or nitro (hereinafter referred to as “Cring is C-6”),

a compound wherein C ring is C-5 and G¹ and G² are each independently CHor N (hereinafter referred to as “C ring is C-7”),

a compound wherein C ring is C-6 and G¹ and G² are each independently CHor N (hereinafter referred to as “C ring is C-8”),

a compound wherein C ring is

 

 (hereinafter referred to as “C ring is C-9”)

a compound wherein X and X′ are —O—, —CH₂—, —NR¹— (wherein R¹ ishydrogen, optionally substituted lower alkyl, lower alkenyl, loweralkylcarbonyl or optionally substituted lower alkoxycarbonyl) or —S(O)p—wherein p is an integer of 0-2,

Y and Y′ are each independently optionally substituted lower alkyl,optionally substituted lower alkenyl, optionally substituted loweralkynyl, optionally substituted cycloalkyl, optionally substitutedcycloalkenyl, optionally substituted amino, optionally substitutedsulfamoyl, optionally substituted aryl or optionally substituted 5- or6-membered heterocycle,

Y may be optionally substituted lower alkoxycarbonyl, optionallysubstituted lower alkylsulfonyl or optionally substituted arylsulfonylwhen X is —O— or —NR¹—,

Y′ may be optionally substituted lower alkoxycarbonyl, optionallysubstituted lower alkylsulfonyl or optionally substituted arylsulfonylwhen X′ is —O— or —NR¹—,

Y may be hydrogen or halogen when X is —CH₂— or NR¹ and Y′ may behydrogen or halogen when X′ is —CH₂— or —NR¹— provided that Y and Y′ arenot simultaneously hydrogen (hereinafter referred to as “X, X′, Y and Y′are XY-1”),

a compound wherein X and X′ are each independently —O—, —CH₂—, —NR¹—wherein R¹ is hydrogen, optionally substituted lower alkyl, loweralkenyl, lower alkylcarbonyl or optionally substituted loweralkoxycarbonyl or —S(O)p— wherein p is an integer of 0-2,

Y and Y′ are each independently optionally substituted lower alkyl,optionally substituted lower alkenyl, optionally substituted loweralkynyl, optionally substituted cycloalkyl, optionally substitutedsulfamoyl, optionally substituted aryl or optionally substituted 5- or6-membered heterocycle hereinafter referred to as “X, X′, Y and Y′ areXY-2”),

a compound wherein one of X and X′ is —O— and the other is —NR¹— whereinR¹ is hydrogen, optionally substituted lower alkyl, lower alkenyl, loweralkylcarbonyl or optionally substituted lower alkoxycarbonyl(hereinafter referred to as “X, X′, Y and Y′ are XY-3”),

a compound wherein one of X and X′ is —O— and the other is —NH—(hereinafter referred to as “X, X′, Y and Y′ are XY-4”),

a compound wherein at least one of Y and Y′ is prenyl (hereinafterreferred to as “X, X′, Y and Y′ are XY-5”),

a compound wherein X and X′ are each independently —O— or —NR¹— whereinR¹ is hydrogen, lower alkyl, lower alkenyl or optionally substitutedlower alkoxycarbonyl, Y and Y′ are each independently optionallysubstituted lower alkyl, optionally substituted lower alkenyl,optionally substituted lower alkynyl, optionally substituted cycloalkyl,optionally substituted sulfamoyl, optionally substituted aryl oroptionally substituted 5- or 6-membered heterocycle (hereinafterreferred to as “X, X′, Y and Y′ are XY-6”),

a compound wherein one of X and X′ is —O— and the other is —NR¹— whereinR¹ is hydrogen, lower alkyl, lower alkenyl or optionally substitutedlower alkoxycarbonyl, Y and Y′ are each independently optionallysubstituted lower alkyl, optionally substituted lower alkenyl oroptionally substituted lower alkynyl (hereinafter referred to as “X, X′,Y and Y′ are XY-7”),

a compound wherein one of X and X′ is —O— and the other is —NH, Y and Y′are each independently optionally substituted lower alkyl, optionallysubstituted lower alkenyl, optionally substituted alkynyl, optionallysubstituted cycloalkyl, optionally substituted sulfamoyl, optionallysubstituted aryl or optionally substituted 5- or 6-membered heterocycle(hereinafter referred to as “X, X′, Y and Y′ are XY-8”),

a compound wherein one of X and X′ is —O— and the other is —NR¹— whereinR¹ is hydrogen, lower alkyl or lower alkenyl, Y and Y′ are eachindependently optionally substituted lower alkyl, or optionallysubstituted lower alkenyl (hereinafter referred to as “X, X′, Y and Y′are XY-9”),

a compound wherein one of X and X′ is —O— and the other is —NH—, Y andY′ are each independently optionally substituted lower alkyl oroptionally substituted lower alkenyl (hereinafter referred to as “X, X′,Y and Y′ are XY-10”),

a compound wherein one of X and X′ is —O— and the other is —NR¹— whereinR¹ is hydrogen, lower alkyl, lower alkenyl or optionally substitutedlower alkoxycarbonyl, one of Y and Y′ is lower alkyl or lower alkenyland the other is optionally substituted lower alkyl, optionallysubstituted lower alkenyl, optionally substituted lower alkynyl,optionally substituted cycloalkyl, optionally substituted sulfamoyl,optionally substituted aryl or optionally substituted 5- or 6-memberedheterocycle (hereinafter referred to as “X, X′, Y and Y′ are XY-11”),

a compound wherein one of X and X′ is —O— and the other is —NH—, one ofY and Y′ is lower alkyl or lower alkenyl and the other is optionallysubstituted lower alkyl, optionally substituted lower alkenyl,optionally substituted lower alkynyl, optionally substituted cycloalkyl,optionally substituted sulfamoyl, optionally substituted aryl oroptionally substituted 5- or 6-membered heterocycle (hereinafterreferred to as “X, X′, Y and Y′ are XY-12”),

a compound wherein one of X and X′ is —O— and the other is —NR¹— whereinR¹ is hydrogen, lower alkyl, lower alkenyl or optionally substitutedlower alkoxycarbonyl, one of Y and Y′ is lower alkyl or lower alkenyland the other is hydrogen or optionally substituted lower alkyl,optionally substituted lower alkenyl or optionally substituted loweralkynyl (hereinafter referred to as “X, X′, Y and Y′ are XY-13”),

a compound wherein one of X and X′ is —O— and the other is —NH—, one ofY and Y′ is lower alkyl or lower alkenyl and the other is hydrogen,optionally substituted lower alkyl, optionally substituted lower alkenylor optionally substituted lower alkynyl (hereinafter referred to as “X,X′, Y and Y′ are XY-14”),

a compound wherein one of X and X′ is —O— and the other is —NR¹— whereinR¹ is hydrogen, lower alkyl, lower alkenyl or optionally substitutedlower alkoxycarbonyl, one of Y and Y′ is prenyl and the other isoptionally substituted lower alkyl, optionally substituted loweralkenyl, optionally substituted lower alkynyl, optionally substitutedcycloalkyl, optionally substituted sulfamoyl, optionally substitutedaryl or optionally substituted 5- or 6-membered heterocycle (hereinafterreferred to as “X, X′, Y and Y′ are XY-15”),

a compound wherein one of X and X′ is —O— and the other is —NH—, one ofY and Y′ is prenyl and the other is optionally substituted lower alkyl,optionally substituted lower alkenyl, optionally substituted loweralkynyl, optionally substituted cycloalkyl, optionally substitutedsulfamoyl, optionally substituted aryl or optionally substituted 5- or6-membered heterocycle (hereinafter referred to as “X, X′, Y and Y′ areXY-16”),

a compound wherein one of X and X′ is —O— and the other is —NR¹— whereinR¹ is hydrogen, lower alkyl, lower alkenyl or optionally substitutedlower alkoxycarbonyl, one of Y and Y′ is prenyl and the other ishydrogen, optionally substituted lower alkyl, optionally substitutedlower alkenyl or optionally substituted lower alkynyl (hereinafterreferred to as “X, X′, Y and Y′ are XY-17”),

a compound wherein one of X and X′ is —O— and the other is —NH—, one ofY and Y′ is prenyl and the other is hydrogen, optionally substitutedlower alkyl, optionally substituted lower alkenyl or optionallysubstituted lower alkynyl (hereinafter referred to as “X, X′, Y and Y′are XY-18”),

a compound wherein one of —X—Y and —X′—Y′ is optionally substitutedlower alkylamino or optionally substituted lower alkenylamino and theother is optionally substituted lower alkoxy or optionally substitutedlower alkenyloxy (hereinafter referred to as “X, X′, Y and Y′ areXY-19”),

a compound wherein one of —X—Y and —X′—Y′ is optionally substitutedlower alkylamino or optionally substituted lower alkenylamino and theother is prenyloxy (hereinafter referred to as “X, X′, Y and Y′ areXY-20”),

a compound wherein R⁴ and R⁵ are R45-1 and R⁶ and R⁷ are R67-1,

a compound wherein R⁴ and R⁵ are R45-1 and R⁶ and R⁷ are R67-2,

a compound wherein R⁴ and R⁵ are R45-2 and R⁶ and R⁷ are R67-1,

a compound wherein R⁴ and R⁵ are R45-2 and R⁶ and R⁷ are R67-2,

a compound wherein R⁴ and R⁵ are R45-3 and R⁶ and R⁷ are R67-1,

a compound wherein R⁴ and R⁵ are R45-3 and R⁶ and R⁷ are R67-2,

a compound wherein R⁴ and R⁵ are R45-4 and R⁶ and R⁷ are R67-1,

a compound wherein R⁴ and R⁵ are R45-4 and R⁶ and R⁷ are R67-2,

a compound wherein R⁴ and R⁵ are R45-5 and R⁶ and R⁷ are R67-1,

a compound wherein R⁴ and R⁵ are R45-5 and R⁶ and R⁷ are R67-2,

a compound wherein R⁴ and R⁵ are R45-6 and R⁶ and R⁷ are R67-1,

a compound wherein R⁴ and R⁵ are R45-6 and R⁶ and R⁷ are R67-2,

a compound wherein R⁴ and R⁵ are R45-7 and R⁶ and R⁷ are R67-1,

a compound wherein R⁴ and R⁵ are R45-7 and R⁶ and R⁷ are R67-2,

a compound wherein R⁸ and R¹¹ are R811-2 and R⁹ and R¹⁰ are R910-3,

a compound wherein R⁸ and R¹¹ are R811-2 and R⁹ and R¹⁰ are R910-4,

a compound wherein R⁸ and R¹¹ are R811-2 and R⁹ and R¹⁰ are R910-5,

a compound wherein R⁸ and R¹¹ are R811-2 and R⁹ and R¹⁰ are R910-6,

a compound wherein R⁸ and R¹¹ are R811-2 and R⁹ and R¹⁰ are R910-7,

a compound wherein R⁸ and R¹¹ are R811-2 and R⁹ and R¹⁰ are R910-8,

a compound wherein R⁸ and R¹¹ are R811-2 and R⁹ and R¹⁰ are R910-9,

a compound wherein R⁸ and R¹¹ are R811-2 and R⁹ and R¹⁰ are R910-10,

a compound wherein R⁸ and R¹¹ are R811-2 and R⁹ and R¹⁰ are R910-11,

a compound wherein R⁸ and R¹¹ are R811-3 and R⁹ and R¹⁰ are R910-3,

a compound wherein R⁸ and R¹¹ are R811-3 and R⁹ and R¹⁰ are R910-4,

a compound wherein R⁸ and R¹¹ are R811-3 and R⁹ and R¹⁰ are R910-5,

a compound wherein R⁸ and R¹¹ are R811-3 and R⁹ and R¹⁰ are R910-6,

a compound wherein R⁸ and R¹¹ are R811-3 and R⁹ and R¹⁰ are R910-7,

a compound wherein R⁸ and R¹¹ are R811-3 and R⁹ and R¹⁰ are R910-8,

a compound wherein R⁸ and R¹¹ are R811-3 and R⁹ and R¹⁰ are R910-9,

a compound wherein R⁸ and R¹¹ are R811-3 and R⁹ and R¹⁰ are R910-10,

a compound wherein R⁸ and R¹¹ are R811-3 and R⁹ and R¹⁰ are R910-11,

a compound wherein R⁸ and R¹¹ are R811-4 and R⁹ and R¹⁰ are R910-3,

a compound wherein R⁸ and R¹¹ are R811-4 and R⁹ and R¹⁰ are R910-4,

a compound wherein R⁸ and R¹¹ are R811-4 and R⁹ and R¹⁰ are R910-5,

a compound wherein R⁸ and R¹¹ are R811-4 and R⁹ and R¹⁰ are R910-6,

a compound wherein R⁸ and R¹¹ are R811-4 and R⁹ and R¹⁰ are R910-7,

a compound wherein R⁸ and R¹¹ are R811-4 and R⁹ and R¹⁰ are R910-8,

a compound wherein R⁸ and R¹¹ are R811-4 and R⁹ and R¹⁰ are R910-9,

a compound wherein R⁸ and R¹¹ are R811-4 and R⁹ and R¹⁰ are R910-10,

a compound wherein R⁸ and R¹¹ are R811-4 and R⁹ and R¹⁰ are R910-11,

a compound wherein R⁸ and R¹¹ are R811-5 and R⁹ and R¹⁰ are R910-1,

a compound wherein R⁸ and R¹¹ are R811-5 and R⁹ and R¹⁰ are R910-2,

a compound wherein R⁸ and R¹¹ are R811-5 and R⁹ and R¹⁰ are R910-3,

a compound wherein R⁸ and R¹¹ are R811-5 and R⁹ and R¹⁰ are R910-4,

a compound wherein R⁸ and R¹¹ are R811-5 and R⁹ and R¹⁰ are R910-5,

a compound wherein R⁸ and R¹¹ are R811-5 and R⁹ and R¹⁰ are R910-6,

a compound wherein R⁸ and R¹¹ are R811-5 and R⁹ and R¹⁰ are R910-7,

a compound wherein R⁸ and R¹¹ are R811-5 and R⁹ and R¹⁰ are R910-8,

a compound wherein R⁸ and R¹¹ are R811-5 and R⁹ and R¹⁰ are R910-9,

a compound wherein R⁸ and R¹¹ are R811-5 and R⁹ and R¹⁰ are R910-10,

a compound wherein R⁸ and R¹¹ are R811-5 and R⁹ and R¹⁰ are R910-11,

a compound wherein R⁸ and R¹¹ are R811-6 and R⁹ and R¹⁰ are R910-1,

a compound wherein R⁸ and R¹¹ are R811-6 and R⁹ and R10 are R910-2,

a compound wherein R⁸ and R¹¹ are R811-6 and R⁹ and R¹⁰ are R910-3,

a compound wherein R⁸ and R¹¹ are R811-6 and R⁹ and R¹⁰ are R910-4,

a compound wherein R⁸ and R¹¹ are R811-6 and R⁹ and R¹⁰ are R910-5,

a compound wherein R⁸ and R¹¹ are R811-6 and R⁹ and R¹⁰ are R910-6,

a compound wherein R⁸ and R¹¹ are R811-6 and R⁹ and R¹⁰ are R910-7,

a compound wherein R⁸ and R¹¹ are R811-6 and R⁹ and R¹⁰ are R910-8,

a compound wherein R⁸ and R¹¹ are R811-6 and R⁹ and R¹⁰ are R910-9,

a compound wherein R⁸ and R¹¹ are R811-6 and R⁹ and R¹⁰ are R910-10,

a compound wherein R⁸ and R¹¹ are R811-6 and R⁹ and R¹⁰ are R910-11,

a compound wherein R⁸ and R¹¹ are R811-7 and R⁹ and R¹⁰ are R910-1,

a compound wherein R⁸ and R¹¹ are R811-7 and R⁹ and R¹⁰ are R910-2,

a compound wherein R⁸ and R¹¹ are R811-7 and R⁹ and R¹⁰ are R910-3,

a compound wherein R⁸ and R¹¹ are R811-7 and R⁹ and R¹⁰ are R910-4,

a compound wherein R⁸ and R¹¹ are R811-7 and R⁹ and R¹⁰ are R910-5,

a compound wherein R⁸ and R¹¹ are R811-7 and R⁹ and R¹⁰ are R910-6,

a compound wherein R⁸ and R¹¹ are R811-7 and R⁹ and R¹⁰ are R910-7,

a compound wherein R⁸ and R¹¹ are R811-7 and R⁹ and R¹⁰ are R910-8,

a compound wherein R⁸ and R¹¹ are R811-7 and R⁹ and R¹⁰ are R910-9,

a compound wherein R⁸ and R¹¹ are R811-7 and R⁹ and R¹⁰ are R910-10,

a compound wherein R⁸ and R¹¹ are R811-7 and R⁹ and R¹⁰ are R910-11,

a compound wherein R⁸ and R¹¹ are R811-8 and R⁹ and R¹⁰ are R910-1,

a compound wherein R⁸ and R¹¹ are R811-8 and R⁹ and R¹⁰ are R910-2,

a compound wherein R⁸ and R¹¹ are R811-8 and R⁹ and R¹⁰ are R910-3,

a compound wherein R⁸ and R¹¹ are R811-8 and R⁹ and R¹⁰ are R910-4,

a compound wherein R⁸ and R¹¹ are R811-8 and R⁹ and R¹⁰ are R910-5,

a compound wherein R⁸ and R¹¹ are R811-8 and R⁹ and R¹⁰ are R910-6,

a compound wherein R⁸ and R¹¹ are R811-8 and R⁹ and R¹⁰ are R910-7,

a compound wherein R⁸ and R¹¹ are R811-8 and R⁹ and R¹⁰ are R910-8,

a compound wherein R⁸ and R¹¹ are R811-8 and R⁹ and R¹⁰ are R910-9,

a compound wherein R⁸ and R¹¹ are R811-8 and R⁹ and R¹⁰ are R910-10,

a compound wherein R⁸ and R¹¹ are R811-8 and R⁹ and R¹⁰ are R910-11,

a compound wherein R⁸ and R¹¹ are R811-9 and R⁹ and R¹⁰ are R910-1,

a compound wherein R⁸ and R¹¹ are R811-9 and R⁹ and R¹⁰ are R910-2,

a compound wherein R⁸ and R¹¹ are R811-9 and R⁹ and R¹⁰ are R910-3,

a compound wherein R⁸ and R¹¹ are R811-9 and R⁹ and R¹⁰ are R910-4,

a compound wherein R⁸ and R¹¹ are R811-9 and R⁹ and R¹⁰ are R910-5,

a compound wherein R⁸ and R¹¹ are R811-9 and R⁹ and R¹⁰ are R910-6,

a compound wherein R⁸ and R¹¹ are R811-9 and R⁹ and R¹⁰ are R910-7,

a compound wherein R⁸ and R¹¹ are R811-9 and R⁹ and R¹⁰ are R910-8,

a compound wherein R⁸ and R¹¹ are R811-9 and R⁹ and R¹⁰ are R910-9,

a compound wherein R⁸ and R¹¹ are R811-9 and R⁹ and R¹⁰ are R910-10,

a compound wherein R⁸ and R¹¹ are R811-9 and R⁹ and R¹⁰ are R910-11,

a compound wherein R⁸ and R¹¹ are R811-10 and R⁹ and R¹⁰ are R910-1,

a compound wherein R⁸ and R¹¹ are R811-10 and R⁹ and R¹⁰ are R910-2,

a compound wherein R⁸ and R¹¹ are R811-10 and R⁹ and R¹⁰ are R910-3,

a compound wherein R⁸ and R¹¹ are R811-10 and R⁹ and R¹⁰ are R910-4,

a compound wherein R⁸ and R¹¹ are R811-10 and R⁹ and R¹⁰ are R910-5,

a compound wherein R⁸ and R¹¹ are R811-10 and R⁹ and R¹⁰ are R910-6,

a compound wherein R⁸ and R¹¹ are R811-10 and R⁹ and R¹⁰ are R910-7,

a compound wherein R⁸ and R¹¹ are R811-10 and R⁹ and R¹⁰ are R910-8,

a compound wherein R⁸ and R¹¹ are R811-10 and R⁹ and R¹⁰ are R910-9,

a compound wherein R⁸ and R¹¹ are R811-10 and R⁹ and R¹⁰ are R910-10,

a compound wherein R⁸ and R¹¹ are R811-10 and R⁹ and R¹⁰ are R910-11,

a compound wherein R⁸ and R¹¹ are R811-11 and R⁹ and R¹⁰ are R910-1,

a compound wherein R⁸ and R¹¹ are R811-11 and R⁹ and R¹⁰ are R910-2,

a compound wherein R⁸ and R¹¹ are R811-11 and R⁹ and R¹⁰ are R910-3,

a compound wherein R⁸ and R¹¹ are R811-11 and R⁹ and R¹⁰ are R910-4,

a compound wherein R⁸ and R¹¹ are R811-11 and R⁹ and R¹⁰ are R910-5,

a compound wherein R⁸ and R¹¹ are R811-11 and R⁹ and R¹⁰ are R910-6,

a compound wherein R⁸ and R¹¹ are R811-11 and R⁹ and R¹⁰ are R910-7,

a compound wherein R⁸ and R¹¹ are R811-11 and R⁹ and R¹⁰ are R910-8,

a compound wherein R⁸ and R¹¹ are R811-11 and R⁹ and R¹⁰ are R910-9,

a compound wherein R⁸ and R¹¹ are R811-11 and R⁹ and R¹⁰ are R910-10,

a compound wherein R⁸ and R¹¹ are R811-11 and R⁹ and R¹⁰ are R910-11,

a compound wherein R⁸ and R¹¹ are R811-12 and R⁹ and R¹⁰ are R910-1,

a compound wherein R⁸ and R¹¹ are R811-12 and R⁹ and R¹⁰ are R910-2,

a compound wherein R⁸ and R¹¹ are R811-12 and R⁹ and R¹⁰ are R910-3,

a compound wherein R⁸ and R¹¹ are R811-12 and R⁹ and R¹⁰ are R910-4,

a compound wherein R⁸ and R¹¹ are R811-12 and R⁹ and R¹⁰ are R910-5,

a compound wherein R⁸ and R¹¹ are R811-12 and R⁹ and R¹⁰ are R910-6,

a compound wherein R⁸ and R¹¹ are R811-12 and R⁹ and R¹⁰ are R910-7,

a compound wherein R⁸ and R¹¹ are R811-12 and R⁹ and R¹⁰ are R910-8,

a compound wherein R⁸ and R¹¹ are R811-12 and R⁹ and R¹⁰ are R910-9,

a compound wherein R⁸ and R¹¹ are R811-12 and R⁹ and R¹⁰ are R910-10,

a compound wherein R⁸ and R¹¹ are R811-12 and R⁹ and R¹⁰ are R910-11,

a compound wherein R⁴ and R⁵ are R45-1 and R⁸ and R¹¹ are R811-3,

a compound wherein R⁴ and R⁵ are R45-1 and R⁸ and R¹¹ are R811-4,

a compound wherein R⁴ and R⁵ are R45-1 and R⁸ and R¹¹ are R811-5,

a compound wherein R⁴ and R⁵ are R45-1 and R⁸ and R¹¹ are R811-6,

a compound wherein R⁴ and R⁵ are R45-1 and R⁸ and R¹¹ are R811-7,

a compound wherein R⁴ and R⁵ are R45-1 and R⁸ and R¹¹ are R811-8,

a compound wherein R⁴ and R⁵ are R45-1 and R⁸ and R¹¹ are R811-9,

a compound wherein R⁴ and R⁵ are R45-1 and R⁸ and R¹¹ are R811-10,

a compound wherein R⁴ and R⁵ are R45-1 and R⁸ and R¹¹ are R811-11,

a compound wherein R⁴ and R⁵ are R45-1 and R⁸ and R¹¹ are R811-12,

a compound wherein R⁴ and R⁵ are R45-2 and R⁸ and R¹¹ are R811-3,

a compound wherein R⁴ and R⁵ are R45-2 and R⁸ and R¹¹ are R811-4,

a compound wherein R⁴ and R⁵ are R45-2 and R⁸ and R¹¹ are R811-5,

a compound wherein R⁴ and R⁵ are R45-2 and R⁸ and R¹¹ are R811-6,

a compound wherein R⁴ and R⁵ are R45-2 and R⁸ and R¹¹ are R811-7,

a compound wherein R⁴ and R⁵ are R45-2 and R⁸ and R¹¹ are R811-8,

a compound wherein R⁴ and R⁵ are R45-2 and R⁸ and R¹¹ are R811-9,

a compound wherein R⁴ and R⁵ are R45-2 and R⁸ and R¹¹ are R811-10,

a compound wherein R⁴ and R⁵ are R45-2 and R⁸ and R¹¹ are R811-11,

a compound wherein R⁴ and R⁵ are R45-2 and R⁸ and R¹¹ are R811-12,

a compound wherein R⁴ and R⁵ are R45-3 and R⁸ and R¹¹ are R811-1,

a compound wherein R⁴ and R⁵ are R45-3 and R⁸ and R¹¹ are R811-2,

a compound wherein R⁴ and R⁵ are R45-3 and R⁸ and R¹¹ are R811-3,

a compound wherein R⁴ and R⁵ are R45-3 and R⁸ and R¹¹ are R811-4,

a compound wherein R⁴ and R⁵ are R45-3 and R⁸ and R¹¹ are R811-5,

a compound wherein R⁴ and R⁵ are R45-3 and R⁸ and R¹¹ are R811-6,

a compound wherein R⁴ and R⁵ are R45-3 and R⁸ and R¹¹ are R811-7,

a compound wherein R⁴ and R⁵ are R45-3 and R⁸ and R¹¹ are R811-8,

a compound wherein R⁴ and R⁵ are R45-3 and R⁸ and R¹¹ are R811-9,

a compound wherein R⁴ and R⁵ are R45-3 and R⁸ and R¹¹ are R811-10,

a compound wherein R⁴ and R⁵ are R45-3 and R⁸ and R¹¹ are R811-11,

a compound wherein R⁴ and R⁵ are R45-3 and R⁸ and R¹¹ are R811-12,

a compound wherein R⁴ and R⁵ are R45-4 and R⁸ and R¹¹ are R811-1,

a compound wherein R⁴ and R⁵ are R45-4 and R⁸ and R¹¹ are R811-2,

a compound wherein R⁴ and R⁵ are R45-4 and R⁸ and R¹¹ are R811-3,

a compound wherein R⁴ and R⁵ are R45-4 and R⁸ and R¹¹ are R811-4,

a compound wherein R⁴ and R⁵ are R45-4 and R⁸ and R¹¹ are R811-5,

a compound wherein R⁴ and R⁵ are R45-4 and R⁸ and R¹¹ are R811-6,

a compound wherein R⁴ and R⁵ are R45-4 and R⁸ and R¹¹ are R811-7,

a compound wherein R⁴ and R⁵ are R45-4 and R⁸ and R¹¹ are R811-8,

a compound wherein R⁴ and R⁵ are R45-4 and R⁸ and R¹¹ are R811-9,

a compound wherein R⁴ and R⁵ are R45-4 and R⁸ and R¹¹ are R811-10,

a compound wherein R⁴ and R⁵ are R45-4 and R⁸ and R¹¹ are R811-11,

a compound wherein R⁴ and R⁵ are R45-4 and R⁸ and R¹¹ are R811-12,

a compound wherein R⁴ and R⁵ are R45-5 and R⁸ and R¹¹ are R811-1,

a compound wherein R⁴ and R⁵ are R45-5 and R⁸ and R¹¹ are R811-2,

a compound wherein R⁴ and R⁵ are R45-5 and R⁸ and R¹¹ are R811-3,

a compound wherein R⁴ and R⁵ are R45-5 and R⁸ and R¹¹ are R811-4,

a compound wherein R⁴ and R⁵ are R45-5 and R⁸ and R¹¹ are R811-5,

a compound wherein R⁴ and R⁵ are R45-5 and R⁸ and R¹¹ are R811-6,

a compound wherein R⁴ and R⁵ are R45-5 and R⁸ and R¹¹ are R811-7,

a compound wherein R⁴ and R⁵ are R45-5 and R⁸ and R¹¹ are R811-8,

a compound wherein R⁴ and R⁵ are R45-5 and R⁸ and R¹¹ are R811-9,

a compound wherein R⁴ and R⁵ are R45-5 and R⁸ and R¹¹ are R811-10,

a compound wherein R⁴ and R⁵ are R45-5 and R⁸ and R¹¹ are R811-11,

a compound wherein R⁴ and R⁵ are R45-5 and R⁸ and R¹¹ are R811-12,

a compound wherein R⁴ and R⁵ are R45-6 and R⁸ and R¹¹ are R811-1,

a compound wherein R⁴ and R⁵ are R45-6 and R⁸ and R¹¹ are R811-2,

a compound wherein R⁴ and R⁵ are R45-6 and R⁸ and R¹¹ are R811-3,

a compound wherein R⁴ and R⁵ are R45-6 and R⁸ and R¹¹ are R811-4,

a compound wherein R⁴ and R⁵ are R45-6 and R⁸ and R¹¹ are R811-5,

a compound wherein R⁴ and R⁵ are R45-6 and R⁸ and R¹¹ are R811-6,

a compound wherein R⁴ and R⁵ are R45-6 and R⁸ and R¹¹ are R811-7,

a compound wherein R⁴ and R⁵ are R45-6 and R⁸ and R¹¹ are R811-8,

a compound wherein R⁴ and R⁵ are R45-6 and R⁸ and R¹¹ are R811-9,

a compound wherein R⁴ and R⁵ are R45-6 and R⁸ and R¹¹ are R811-10,

a compound wherein R⁴ and R⁵ are R45-6 and R⁸ and R¹¹ are R811-11,

a compound wherein R⁴ and R⁵ are R45-6 and R⁸ and R¹¹ are R811-12,

a compound wherein R⁴ and R⁵ are R45-7 and R⁸ and R¹¹ are R811-1,

a compound wherein R⁴ and R⁵ are R45-7 and R⁸ and R¹¹ are R811-2,

a compound wherein R⁴ and R⁵ are R45-7 and R⁸ and R¹¹ are R811-3,

a compound wherein R⁴ and R⁵ are R45-7 and R⁸ and R¹¹ are R811-4,

a compound wherein R⁴ and R⁵ are R45-7 and R⁸ and R¹¹ are R811-5,

a compound wherein R⁴ and R⁵ are R45-7 and R⁸ and R¹¹ are R811-6,

a compound wherein R⁴ and R⁵ are R45-7 and R⁸ and R¹¹ are R811-7,

a compound wherein R⁴ and R⁵ are R45-7 and R⁸ and R¹¹ are R811-8,

a compound wherein R⁴ and R⁵ are R45-7 and R⁸ and R¹¹ are R811-9,

a compound wherein R⁴ and R⁵ are R45-7 and R⁸ and R¹¹ are R811-10,

a compound wherein R⁴ and R⁵ are R45-7 and R⁸ and R¹¹ are R811-11,

a compound wherein R⁴ and R⁵ are R45-7 and R⁸ and R¹¹ are R811-12,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4 and R⁹ and R¹⁰ are R910-3,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4 and R⁹ and R¹⁰ are R910-4,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4 and R⁹ and R¹⁰ are R910-5,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4 and R⁹ and R¹⁰ are R910-8,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-7 and R⁹ and R¹⁰ are R910-3,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-7 and R⁹ and R¹⁰ are R910-4,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-7 and R⁹ and R¹⁰ are R910-5,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-7 and R⁹ and R¹⁰ are R910-8,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10 and R⁹ and R¹⁰ are R910-3,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10 and R⁹ and R¹⁰ are R910-4,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10 and R⁹ and R¹⁰ are R910-5,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10 and R⁹ and R¹⁰ are R910-8,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-12 and R⁹ and R¹⁰ are R910-3,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-12 and R⁹ and R¹⁰ are R910-4,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-12 and R⁹ and R¹⁰ are R910-5,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-12 and R⁹ and R¹⁰ are R910-8,

a compound wherein R⁴ and R⁵ are R45-2, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4 and R⁹ and R¹⁰ are R910-3,

a compound wherein R⁴ and R⁵ are R45-2, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4 and R⁹ and R¹⁰ are R910-4,

a compound wherein R⁴ and R⁵ are R45-2, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4 and R⁹ and R¹⁰ are R910-5,

a compound wherein R⁴ and R⁵ are R45-2, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4 and R⁹ and R¹⁰ are R910-8,

a compound wherein R⁴ and R⁵ are R45-2, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-7 and R⁹ and R¹⁰ are R910-3,

a compound wherein R⁴ and R⁵ are R45-2, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-7 and R⁹ and R¹⁰ are R910-4,

a compound wherein R⁴ and R⁵ are R45-2, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-7 and R⁹ and R¹⁰ are R910-5,

a compound wherein R⁴ and R⁵ are R45-2, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-7 and R⁹ and R¹⁰ are R910-8,

a compound wherein R⁴ and R⁵ are R45-2, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10 and R⁹ and R¹⁰ are R910-3,

a compound wherein R⁴ and R⁵ are R45-2, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10 and R⁹ and R¹⁰ are R910-4,

a compound wherein R⁴ and R⁵ are R45-2, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10 and R⁹ and R¹⁰ are R910-5,

a compound wherein R⁴ and R⁵ are R45-2, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10 and R⁹ and R¹⁰ are R910-8,

a compound wherein R⁴ and R⁵ are R45-2, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-12 and R⁹ and R¹⁰ are R910-3,

a compound wherein R⁴ and R⁵ are R45-2, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-12 and R⁹ and R¹⁰ are R910-4,

a compound wherein R⁴ and R⁵ are R45-2, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-12 and R⁹ and R¹⁰ are R910-5,

a compound wherein R⁴ and R⁵ are R45-2, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-12 and R⁹ and R¹⁰ are R910-8,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4 and R⁹ and R¹⁰ are R910-3,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4 and R⁹ and R¹⁰ are R910-4,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4 and R⁹ and R¹⁰ are R910-5,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4 and R⁹ and R¹⁰ are R910-8,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-7 and R⁹ and R¹⁰ are R910-3,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-7 and R⁹ and R¹⁰ are R910-4,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-7 and R⁹ and R¹⁰ are R910-5,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-7 and R⁹ and R¹⁰ are R910-8,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10 and R⁹ and R¹⁰ are R910-3,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10 and R⁹ and R¹⁰ are R910-4,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10 and R⁹ and R¹⁰ are R910-5,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10 and R⁹ and R¹⁰ are R910-8,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-12 and R⁹ and R¹⁰ are R910-3,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-12 and R⁹ and R¹⁰ are R910-4,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-12 and R⁹ and R¹⁰ are R910-5,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-12 and R⁹ and R¹⁰ are R910-8,

a compound wherein R⁴ and R⁵ are R45-4, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4 and R⁹ and R¹⁰ are R910-3,

a compound wherein R⁴ and R⁵ are R45-4, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4 and R⁹ and R¹⁰ are R910-4,

a compound wherein R⁴ and R⁵ are R45-4, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4 and R⁹ and R¹⁰ are R910-5,

a compound wherein R⁴ and R⁵ are R45-4, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4 and R⁹ and R¹⁰ are R910-8,

a compound wherein R⁴ and R⁵ are R45-4, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-7 and R⁹ and R¹⁰ are R910-3,

a compound wherein R⁴ and R⁵ are R45-4, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-7 and R⁹ and R¹⁰ are R910-4,

a compound wherein R⁴ and R⁵ are R45-4, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-7 and R⁹ and R¹⁰ are R910-5,

a compound wherein R⁴ and R⁵ are R45-4, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-7 and R⁹ and R¹⁰ are R910-8,

a compound wherein R⁴ and R⁵ are R45-4, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10 and R⁹ and R¹⁰ are R910-3,

a compound wherein R⁴ and R⁵ are R45-4, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10 and R⁹ and R¹⁰ are R910-4,

a compound wherein R⁴ and R⁵ are R45-4, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10 and R⁹ and R¹⁰ are R910-5,

a compound wherein R⁴ and R⁵ are R45-4, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10 and R⁹ and R¹⁰ are R910-8,

a compound wherein R⁴ and R⁵ are R45-4, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-12 and R⁹ and R¹⁰ are R910-3,

a compound wherein R⁴ and R⁵ are R45-4, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-12 and R⁹ and R¹⁰ are R910-4,

a compound wherein R⁴ and R⁵ are R45-4, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-12 and R⁹ and R¹⁰ are R910-5,

a compound wherein R⁴ and R⁵ are R45-4, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-12 and R⁹ and R¹⁰ are R910-8,

a compound described in [1] wherein X′ is —O—, —NR¹—, or —S(O)p— and Cring is an optionally substituted 5-membered heterocycle which containsone or two hetero atoms,

a compound wherein R⁴ and R⁵ are R45-4 and C ring is C-1,

a compound wherein R⁸ and R¹¹ are R811-9, R⁹ and R¹⁰ are R910-7 and Cring is C-1,

a compound wherein R⁴ and R⁵ are R45-4 and C ring is C-2,

a compound wherein R⁸ and R¹¹ are R811-9, R⁹ and R¹⁰ are R910-7 and Cring is C-2,

a compound wherein R⁴ and R⁵ are R45-4 and C ring is C-4,

a compound wherein R⁸ and R¹¹ are R811-9, R⁹ and R¹⁰ are R910-7 and Cring is C-4,

a compound wherein X, Y, X′ and Y′ are XY-3 and C ring is C-2,

a compound wherein X, Y, X′ and Y′ are XY-3 and C ring is C-3,

a compound wherein X, Y, X′ and Y′ are XY-3 and C ring is C-4,

a compound wherein X, Y, X′ and Y′ are XY-3 and C ring is C-6,

a compound wherein X, Y, X′ and Y′ are XY-3 and C ring is C-8,

a compound wherein X, Y, X′ and Y′ are XY-3 and C ring is C-9,

a compound wherein X, Y, X′ and Y′ are XY-4 and C ring is C-2,

a compound wherein X, Y, X′ and Y′ are XY-4 and C ring is C-3,

a compound wherein X, Y, X′ and Y′ are XY-4 and C ring is C-4,

a compound wherein X, Y, X′ and Y′ are XY-4 and C ring is C-6,

a compound wherein X, Y, X′ and Y′ are XY-4 and C ring is C-8,

a compound wherein X, Y, X′ and Y′ are XY-4 and C ring is C-9,

a compound wherein X, Y, X′ and Y′ are XY-5 and C ring is C-2,

a compound wherein X, Y, X′ and Y′ are XY-5 and C ring is C-3,

a compound wherein X, Y, X′ and Y′ are XY-5 and C ring is C-4,

a compound wherein X, Y, X′ and Y′ are XY-5 and C ring is C-6,

a compound wherein X, Y, X′ and Y′ are XY-5 and C ring is C-8,

a compound wherein X, Y, X′ and Y′ are XY-5 and C ring is C-9,

a compound wherein X, Y, X′ and Y′ are XY-6 and C ring is C-2,

a compound wherein X, Y, X′ and Y′ are XY-6 and C ring is C-3,

a compound wherein X, Y, X′ and Y′ are XY-6 and C ring is C-4,

a compound wherein X, Y, X′ and Y′ are XY-6 and C ring is C-6,

a compound wherein X, Y, X′ and Y′ are XY-6 and C ring is C-8,

a compound wherein X, Y, X′ and Y′ are XY-6 and C ring is C-9,

a compound wherein X, Y, X′ and Y′ are XY-7 and C ring is C-2,

a compound wherein X, Y, X′ and Y′ are XY-7 and C ring is C-3,

a compound wherein X, Y, X′ and Y′ are XY-7 and C ring is C-4,

a compound wherein X, Y, X′ and Y′ are XY-7 and C ring is C-6,

a compound wherein X, Y, X′ and Y′ are XY-7 and C ring is C-8,

a compound wherein X, Y, X′ and Y′ are XY-7 and C ring is C-9,

a compound wherein X, Y, X′ and Y′ are XY-8 and C ring is C-2,

a compound wherein X, Y, X′ and Y′ are XY-8 and C ring is C-3,

a compound wherein X, Y, X′ and Y′ are XY-8 and C ring is C-4,

a compound wherein X, Y, X′ and Y′ are XY-8 and C ring is C-6,

a compound wherein X, Y, X′ and Y′ are XY-8 and C ring is C-8,

a compound wherein X, Y, X′ and Y′ are XY-8 and C ring is C-9,

a compound wherein X, Y, X′ and Y′ are XY-9 and C ring is C-2,

a compound wherein X, Y, X′ and Y′ are XY-9 and C ring is C-3,

a compound wherein X, Y, X′ and Y′ are XY-9 and C ring is C-4,

a compound wherein X, Y, X′ and Y′ are XY-9 and C ring is C-6,

a compound wherein X, Y, X′ and Y′ are XY-9 and C ring is C-8,

a compound wherein X, Y, X′ and Y′ are XY-9 and C ring is C-9,

a compound wherein X, Y, X′ and Y′ are XY-10 and C ring is C-2,

a compound wherein X, Y, X′ and Y′ are XY-10 and C ring is C-3,

a compound wherein X, Y, X′ and Y′ are XY-10 and C ring is C-4,

a compound wherein X, Y, X′ and Y′ are XY-10 and C ring is C-6,

a compound wherein X, Y, X′ and Y′ are XY-10 and C ring is C-8,

a compound wherein X, Y, X′ and Y′ are XY-10 and C ring is C-9,

a compound wherein X, Y, X′ and Y′ are XY-11 and C ring is C-2,

a compound wherein X, Y, X′ and Y′ are XY-11 and C ring is C-3,

a compound wherein X, Y, X′ and Y′ are XY-11 and C ring is C-4,

a compound wherein X, Y, X′ and Y′ are XY-11 and C ring is C-6,

a compound wherein X, Y, X′ and Y′ are XY-11 and C ring is C-8,

a compound wherein X, Y, X′ and Y′ are XY-11 and C ring is C-9,

a compound wherein X, Y, X′ and Y′ are XY-12 and C ring is C-2,

a compound wherein X, Y, X′ and Y′ are XY-12 and C ring is C-3,

a compound wherein X, Y, X′ and Y′ are XY-12 and C ring is C-4,

a compound wherein X, Y, X′ and Y′ are XY-12 and C ring is C-6,

a compound wherein X, Y, X′ and Y′ are XY-12 and C ring is C-8,

a compound wherein X, Y, X′ and Y′ are XY-12 and C ring is C-9,

a compound wherein X, Y, X′ and Y′ are XY-13 and C ring is C-2,

a compound wherein X, Y, X′ and Y′ are XY-13 and C ring is C-3,

a compound wherein X, Y, X′ and Y′ are XY-13 and C ring is C-4,

a compound wherein X, Y, X′ and Y′ are XY-13 and C ring is C-6,

a compound wherein X, Y, X′ and Y′ are XY-13 and C ring is C-8,

a compound wherein X, Y, X′ and Y′ are XY-13 and C ring is C-9,

a compound wherein X, Y, X′ and Y′ are XY-14 and C ring is C-2,

a compound wherein X, Y, X′ and Y′ are XY-14 and C ring is C-3,

a compound wherein X, Y, X′ and Y′ are XY-14 and C ring is C-4,

a compound wherein X, Y, X′ and Y′ are XY-14 and C ring is C-6,

a compound wherein X, Y, X′ and Y′ are XY-14 and C ring is C-8,

a compound wherein X, Y, X′ and Y′ are XY-14 and C ring is C-9,

a compound wherein X, Y, X′ and Y′ are XY-15 and C ring is C-2,

a compound wherein X, Y, X′ and Y′ are XY-15 and C ring is C-3,

a compound wherein X, Y, X′ and Y′ are XY-15 and C ring is C-4,

a compound wherein X, Y, X′ and Y′ are XY-15 and C ring is C-6,

a compound wherein X, Y, X′ and Y′ are XY-15 and C ring is C-8,

a compound wherein X, Y, X′ and Y′ are XY-15 and C ring is C-9,

a compound wherein X, Y, X′ and Y′ are XY-16 and C ring is C-2,

a compound wherein X, Y, X′ and Y′ are XY-16 and C ring is C-3,

a compound wherein X, Y, X′ and Y′ are XY-16 and C ring is C-4,

a compound wherein X, Y, X′ and Y′ are XY-16 and C ring is C-6,

a compound wherein X, Y, X′ and Y′ are XY-16 and C ring is C-8,

a compound wherein X, Y, X′ and Y′ are XY-16 and C ring is C-9,

a compound wherein X, Y, X′ and Y′ are XY-17 and C ring is C-2,

a compound wherein X, Y, X′ and Y′ are XY-17 and C ring is C-3,

a compound wherein X, Y, X′ and Y′ are XY-17 and C ring is C-4,

a compound wherein X, Y, X′ and Y′ are XY-17 and C ring is C-6,

a compound wherein X, Y, X′ and Y′ are XY-17 and C ring is C-8,

a compound wherein X, Y, X′ and Y′ are XY-17 and C ring is C-9,

a compound wherein X, Y, X′ and Y′ are XY-18 and C ring is C-2,

a compound wherein X, Y, X′ and Y′ are XY-18 and C ring is C-3,

a compound wherein X, Y, X′ and Y′ are XY-18 and C ring is C-4,

a compound wherein X, Y, X′ and Y′ are XY-18 and C ring is C-6,

a compound wherein X, Y, X′ and Y′ are XY-18 and C ring is C-8,

a compound wherein X, Y, X′ and Y′ are XY-18 and C ring is C-9,

a compound wherein X, Y, X′ and Y′ are XY-19 and C ring is C-2,

a compound wherein X, Y, X′ and Y′ are XY-19 and C ring is C-3,

a compound wherein X, Y, X′ and Y′ are XY-19 and C ring is C-4,

a compound wherein X, Y, X′ and Y′ are XY-19 and C ring is C-6,

a compound wherein X, Y, X′ and Y′ are XY-19 and C ring is C-8,

a compound wherein X, Y, X′ and Y′ are XY-19 and C ring is C-9,

a compound wherein X, Y, X′ and Y′ are XY-20 and C ring is C-2,

a compound wherein X, Y, X′ and Y′ are XY-20 and C ring is C-3,

a compound wherein X, Y, X′ and Y′ are XY-20 and C ring is C-4,

a compound wherein X, Y, X′ and Y′ are XY-20 and C ring is C-6,

a compound wherein X, Y, X′ and Y′ are XY-20 and C ring is C-8,

a compound wherein X, Y, X′ and Y′ are XY-20 and C ring is C-9,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4 R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-5 and C ring isC-3,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-5 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-5 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-5 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-6 and C ringis C-3,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-6 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-6 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-6 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-9 and C ringis C-3,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-9 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-9 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-9 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-17 and C ringis C-3,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-17 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-17 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-17 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-5 and C ringis C-3,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-5 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-5 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-5 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹¹ are R910-5, X, Y, X′ and Y′ are XY-6 and C ringis C-3,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-6 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-6 and C ringis C-6.

a compound wherein R⁴ and R⁵ are R45 1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-6 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-9 and C ringis C-3,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-9 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-9 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-9 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-17 and C ringis C-3,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-17 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-17 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-17 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-5 and C ringis C-3,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-5 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-5 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-5 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-6 and C ringis C-3,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-6 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-6 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-6 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-9 and C ringis C-3,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-9 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-9 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-9 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-17 and C ringis C-3,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-17 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-17 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-17 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-5 and C ringis C-3,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-5 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-5 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-5 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-6 and C ringis C-3,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-6 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-6 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-6 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-9 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-9 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-9 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-17 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-17 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-17 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-5 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-5 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-5 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-6 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-6 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-6 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-9 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-9 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-9 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-17 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-17 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-17 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-5 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-5 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-5 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-6 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-6 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-6 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-9 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-9 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-9 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-17 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-17 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-17 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-5 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-5 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-5 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-6 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-6 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-6 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-9 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-9 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-9 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-17 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-17 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-17 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-5 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-5 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-5 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-6 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-6 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-6 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-9 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-9 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-9 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-17 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-17 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-17 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-5 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-5 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-5 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-6 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-6 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-6 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-9 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-9 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-9 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-17 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-17 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-17 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-5 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-5 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-5 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-6 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-6 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-6 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-9 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-9 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-9 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-17 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-17 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-17 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-5 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-5 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-5 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-6 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-6 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-6 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-9 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-9 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-9 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-17 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-17 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-17 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-5 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-5 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-5 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-6 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-6 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-6 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-9 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-9 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-9 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-17 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-17 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-4, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-17 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-5, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-7 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-5 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-5 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-5 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-6 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-6 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-6 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-9 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-9 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-9 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-17 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-17 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-17 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-5 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-5 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-5 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-6 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-6 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-6 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-9 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-9 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-9 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-17 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-17 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-17 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-5 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-5 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-5 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-6 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-6 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-6 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-9 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-9 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-9 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-17 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-17 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-8, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-17 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-5 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-5 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-5 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-6 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-6 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-6 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-9 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-9 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-9 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-17 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-17 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-4, X, Y, X′ and Y′ are XY-17 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-5 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-5 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-5 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-6 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-6 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-6 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-9 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-9 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-9 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-17 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-17 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-17 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-20 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-20 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-5, X, Y, X′ and Y′ are XY-20 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-5 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-5 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-5 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-6 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-6 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-6 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-9 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-9 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-9 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-17 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-17 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-17 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-17 and C ringis C-9,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-20 and C ringis C-4,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-20 and C ringis C-6,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R⁸ and R¹¹are R811-10, R⁹ and R¹⁰ are R910-7, X, Y, X′ and Y′ are XY-20 and C ringis C-9,

a compound wherein X′ is —O—, —NR¹— or —S(O)p- and C ring is anoptionally substituted 5-membered heterocycle which contains one or twohetero atoms,

a compound wherein C ring is pyridine ring, one of —X—Y and —X′—Y′ is1-pyrolidinyl, 1-piperidinyl, 4-morphorinyl, 4-thiomorpholinyl,optionally substituted 1-piperadinyl (wherein the substituents are loweralkyl or lower alkenyl) or optionally substituted 1-pyrolyl (wherein thesubstituents are lower alkyl), and the other is —NHCH₂CH═CMe₂,—OCH₂CH═CMe₂ or —SCH₂CH═CMe₂,

a compound wherein C ring is pyridine ring, one of —X—Y and —X′—Y′ is1-pyrolidinyl, optionally substituted 1-pyrolyl (wherein thesubstituents are lower alkyl), and the other is —NHCH₂CH═CMe₂,—OCH₂CH═CMe₂ or —SCH₂CH═CMe₂, salt or hydrate thereof.

Another embodiment of the present invention is

[2] a compound of the formula:

 

wherein each symbol is the same as defined in the above [1],

[3] a compound of the formula (Ia′):

 

wherein B ring is optionally substituted 5- or 6-membered heterocyclewhich contains one or two hetero atoms (wherein the substituent ishalogen, hydroxy, optionally substituted lower alkyl, optionallysubstituted lower alkoxy, optionally substituted lower alkenyl,optionally substituted lower alkenyloxy, optionally substituted acyloxy,carboxy, optionally substituted lower alkoxycarbonyl, optionallysubstituted lower alkenyloxycarbonyl, optionally substituted loweralkylthio, optionally substituted lower alkenylthio, optionallysubstituted amino, guanidino, nitro, optionally substituted loweralkylsulfonyl, optionally substituted lower alkylsulfonyloxy, optionallysubstituted arylsulfonyl or optionally substituted arylsulfonyloxy,excluding a compound wherein B ring is substituted with only halogen(s))and W² represents a bond when B ring is 5-membered heterocycle,

X, X′, Y and Y′ are the same defined in [1],

R¹, taken together with Y or Y′, may form —(CH₂)m-, —(CH₂)₂—Q—(CH₂)₂—(wherein Q is CH₂, O, S or NR′), —CR′═CH—CH═CR′—, —CH═N—CH═CH—,—N═CH—N═CH—, —C(═O)—O(CH₂)n-, —C(═O)—NR′—(CH₂)n— or —C(═O)—NR′—N═CH—wherein m is 4 or 5, n is 2 or 3,

R^(′) is hydrogen, lower alkyl or lower alkenyl,

Y may be optionally substituted lower alkoxy when X is —CH₂—,

Y′ may be optionally substituted lower alkoxy when X′ is —CH₂—,

Y may be optionally substituted lower alkoxycarbonyl, optionallysubstituted lower alkylsulfonyl or optionally substituted arylsulfonylwhen X is —O— or —NR¹—, Y′ may be optionally substituted loweralkoxycarbonyl, optionally substituted lower alkylsulfonyl or optionallysubstituted arylsulfonyl when X′ is —O— or —NR¹—,

Y may be hydrogen or halogen when X is —CH₂— or —NR¹—,

Y′ may be hydrogen or halogen when X′ is —CH₂— or —NR¹—,

R⁴, R⁵, R⁶, R⁷, R¹², R¹³, R¹⁴ and R¹⁵ are each independently hydrogen,halogen, hydroxy, optionally substituted lower alkyl, optionallysubstituted lower alkoxy, optionally substituted lower alkenyl,optionally substituted alkenyloxy, optionally substituted acyloxy,carboxy, optionally substituted lower alkoxycarbonyl, optionallysubstituted lower alkenyloxycarbonyl, optionally substituted loweralkylthio, optionally substituted lower alkenylthio, optionallysubstituted amino, optionally substituted carbamoyl, guanidino, nitro,optionally substituted lower alkylsulfonyl, optionally substituted loweralkylsulfonyloxy, optionally substituted arylsulfonyl or optionallysubstituted arylsulfonyloxy, excluding

(i) a compound wherein Y and Y′ are simultaneously hydrogen,

(ii) a compound wherein at least one of Y and Y′ is optionallysubstituted acyl,

(iii) a compound wherein at least one of —X—Y and —X′—Y′ isunsubstituted lower alkoxy, and

(iv) a compound wherein —X—Y and —X′—Y′ are simultaneously optionallysubstituted lower alkoxy or amino substituted with phenyl,

salt or hydrate thereof.

The following compounds of (Ia′), salt or hydrate thereof are morepreferable.

a compound wherein R⁴ and R⁵ are R45-1,

a compound wherein R⁴ and R⁵ are R45-2,

a compound wherein R⁴ and R⁵ are R45-3,

a compound wherein R⁴ and R⁵ are R45-4,

a compound wherein R⁴ and R⁵ are R45-5,

a compound wherein R⁴ and R⁵ are R45-6,

a compound wherein R⁴ and R⁵ are R45-7,

a compound wherein R⁶ and R⁷ are R67-1,

a compound wherein R⁶ and R⁷ are R67-2,

a compound wherein B ring is 5-or ⁶-membered heterocycle which containsat least one N atom (hereinafter referred to as “B ring is B-1”),

a compound wherein B ring is a 6-membered heterocycle which contains atleast one N atom (hereinafter referred to as “B ring is B-2”),

a compound wherein B ring is optionally substituted pyridine, optionallysubstituted pyrimidine, optionally substituted pyridazine or optionallysubstituted pyrazine (hereinafter referred to as “B ring is B-3”),

a compound wherein B ring is optionally substituted pyridine oroptionally substituted pyrimidine (hereinafter referred to as “B ring isB-4”),

a compound wherein B ring is optionally substituted pyridine oroptionally substituted pyrimidine (wherein the substituents areoptionally substituted lower alkyl or optionally substituted loweralkoxy) (hereinafter referred to as “B ring is B-5”),

a compound wherein B ring is optionally substituted pyridine wherein “Bring is B-6”),

a compound wherein B ring is

 

 wherein G is CH or N, R⁸ and R¹¹ are each independently halogen,hydroxy, optionally substituted lower alkyl, optionally substitutedlower alkoxy, optionally substituted lower alkenyl, optionallysubstituted lower alkenyloxy, optionally substituted acyloxy, carboxy oroptionally substituted lower alkoxycarbonyl (hereinafter referred to as“B ring is B-7”),

a compound wherein R¹², R¹³, R¹⁴ and R¹⁵ are each independentlyhydrogen, hydroxy, halogen, optionally substituted lower alkoxy,optionally substituted acyloxy, optionally substituted loweralkylsulfonyloxy or optionally substituted arylsulfonyloxy (hereinafterreferred to as “R¹², R¹³, R¹⁴, R¹⁵ and R¹⁶ are R12-15-1”),

a compound wherein R¹², R¹³, R¹⁴ and R¹⁵ are each independentlyhydrogen, hydroxy, halogen, lower alkoxy, acyloxy, optionallysubstituted lower alkylsulfonyloxy or arylsulfonyloxy (hereinafterreferred to as “R¹², R¹³, R¹⁴ and R¹⁵ are R12-15-2”),

a compound wherein R¹², R¹³, R¹⁴ and R¹⁵ are each independentlyhydrogen, halogen or lower alkyl (hereinafter referred to as “R¹², R¹³,R¹⁴ and R¹⁵ are 12-15-3”),

a compound wherein R¹², R¹³, R¹⁴ and R¹⁵ are each independentlyhydrogen, chloro or fluoro (hereinafter referred to as “R¹², R¹³, R¹⁴and R¹⁵ are R12-15-4”),

a compound wherein X, Y, X′ and Y′ are XY-1,

a compound wherein X, Y, X′ and Y′ are XY-2,

a compound wherein X, Y, X′ and Y′ are XY-3,

a compound wherein X, Y, X′ and Y′ are XY-4,

a compound wherein X, Y, X′ and Y′ are XY-5,

a compound wherein X, Y, X′ and Y′ are XY-6,

a compound wherein X, Y, X′ and Y′ are XY-7,

a compound wherein X, Y, X′ and Y′ are XY-8,

a compound wherein X, Y, X′ and Y′ are XY-9,

a compound wherein X, Y, X′ and Y′ are XY-10,

a compound wherein X, Y, X′ and Y′ are XY-11,

a compound wherein X, Y, X′ and Y′ are XY-12,

a compound wherein X, Y, X′ and Y′ are XY-13,

a compound wherein X, Y, X′ and Y′ are XY-14,

a compound wherein X, Y, X′ and Y′ are XY-15,

a compound wherein X, Y, X′ and Y′ are XY-16,

a compound wherein X, Y, X′ and Y′ are XY-17,

a compound wherein X, Y, X′ and Y′ are XY-18,

a compound wherein X, Y, X′ and Y′ are XY-19,

a compound wherein X, Y, X′ and Y′ are XY-20,

a compound wherein R⁴ and R⁵ are R45-3 and R⁶ and R⁷ are R67-2,

a compound wherein R⁴ and R⁵ are R45-4 and R⁶ and R⁷ are R67-2,

a compound wherein R⁴ and R⁵ are R45-4 and B ring is B-1,

a compound wherein R⁴ and R⁵ are R45-4 and B ring is B-2,

a compound wherein R⁴ and R⁵ are R45-4 and B ring is B-4,

a compound wherein R⁴ and R⁵ are R45-4 and R¹², R¹³, R¹⁴ and R¹⁵ areR12-15-3,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R¹², R¹³,R¹⁴ and R¹⁵ are R12-15-2, B ring is B-3 and X, X′, Y and Y′ are XY-6,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R¹², R¹³,R¹⁴ and R¹⁵ are R12-15-2, B ring is B-3 and X, X′, Y and Y′ are XY-17,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R¹², R¹³,R¹⁴ and R¹⁵ are R12-15-2, B ring is B-5 and X, X′, Y and Y′ are XY-6,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R¹², R¹³,R¹⁴ and R¹⁵ are R12-15-2, B ring is B-5 and X, X′, Y and Y′ are XY-17,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R¹², R¹³,R¹⁴ and R¹⁵ are R12-15-2, B ring is B-7 and X, X′, Y and Y′ are XY-6,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R¹², R¹³,R¹⁴ and R¹⁵ are R12-15-2, B ring is B-7 and X, X′, Y and Y′ are XY-17,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R¹², R¹³,R¹⁴ and R¹⁵ are R12-15-3, B ring is B-3 and X, X′, Y and Y′ are XY-6,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R¹², R¹³,R¹⁴ and R¹⁵ are R12-15-3, B ring is B-3 and X, X′, Y and Y′ are XY-17,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R¹², R¹³,R¹⁴ and R¹⁵ are R12-15-3, B ring is B-5 and X, X′, Y and Y′ are XY-6,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R¹², R¹³,R¹⁴ and R¹⁵ are R12-15-3, B ring is B-5 and X, X′, Y and Y′ are XY-17,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R¹², R¹³,R¹⁴ and R¹⁵ are R12-15-3, B ring is B-7 and X, X′, Y and Y′ are XY-6,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R¹², R¹³,R¹⁴ and R¹⁵ are R12-15-3, B ring is B-7 and X, X′, Y and Y′ are XY-17,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R¹², R¹³,R¹⁴ and R¹⁵ are R12-15-4, B ring is B-3 and X, X′, Y and Y′ are XY-6,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R¹², R¹³,R¹⁴ and R¹⁵ are R12-15-4, B ring is B-3 and X, X′, Y and Y′ are XY-17,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R¹², R¹³,R¹⁴ and R¹⁵ are R12-15-4, B ring is B-5 and X, X′, Y and Y′ are XY-6,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R¹², R¹³,R¹⁴ and R¹⁵ are R12-15-4, B ring is B-5 and X, X′, Y and Y′ are XY-17,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R¹², R¹³,R¹⁴ and R¹⁵ are R12-15-4, B ring is B-7 and X, X′, Y and Y′ are XY-6,

a compound wherein R⁴ and R⁵ are R45-1, R⁶ and R⁷ are R67-1, R¹², R¹³,R¹⁴ and R¹⁵ are R12-15-4, B ring is B-7 and X, X′, Y and Y′ are XY-17,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R¹², R¹³,R¹⁴ and R¹⁵ are R12-15-2, B ring is B-3 and X, X′, Y and Y′ are XY-6,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R¹², R¹³,R¹⁴ and R¹⁵ are R12-15-2, B ring is B-3 and X, X′, Y and Y′ are XY-17,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R¹², R¹³,R¹⁴ and R¹⁵ are R12-15-3, B ring is B-4 and X, X′, Y and Y′ are XY-6,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R¹², R¹³,R¹⁴ and R¹⁵ are R12-15-2, B ring is B-5 and X, X′, Y and Y′ are XY-6,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R¹², R¹³,R¹⁴ and R¹⁵ are R12-15-2, B ring is B-5 and X, X′, Y and Y′ are XY-17,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R¹², R¹³,R¹⁴ and R¹⁵ are R12-15-2, B ring is B-7 and X, X′, Y and Y′ are XY-6,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R¹², R¹³,R¹⁴ and R¹⁵ are R12-15-2, B ring is B-7 and X, X′, Y and Y′ are XY-17,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R¹², R¹³,R¹⁴ and R¹⁵ are R12-15-3, B ring is B-3 and X, X′, Y and Y′ are XY-6,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R¹², R13,R¹⁴ and R¹⁵ are R12-15-3, B ring is B-3 and X, X′, Y and Y′ are XY-17,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R¹², R¹³,R¹⁴ and R¹⁵ are R12-15-3, B ring is B-5 and X, X′, Y and Y′ are XY-5,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R¹², R¹³,R¹⁴ and R¹⁵ are R12-15-3, B ring is B-5 and X, X′, Y and Y′ are XY-6,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R¹², R13,R¹⁴ and R¹⁵ are R12-15-3, B ring is B-5 and X, X′, Y and Y′ are XY-7,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R¹², R¹³,R¹⁴ and R¹⁵ are R12-15-3, B ring is B-5 and X, X′, Y and Y′ are XY-17,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R¹², R¹³,R¹⁴ and R¹⁵ are R12-15-3, B ring is B-7 and X, X′, Y and Y′ are XY-6,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R¹², R¹³,R¹⁴ and R¹⁵ are R12-15-3, B ring is B-7 and X, X′, Y and Y′ are XY-17,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R¹², R¹³,R¹⁴ and R¹⁵ are R12-15-4, B ring is B-3 and X, X′, Y and Y′ are XY-6,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R¹², R¹³,R¹⁴ and R¹⁵ are R12-15-4, B ring is B-3 and X, X′, Y and Y′ are XY-17,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R¹², R¹³,R¹⁴ and R¹⁵ are R12-15-4, B ring is B-5 and X, X′, Y and X′ are XY-6,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R¹², R¹³,R¹⁴ and R¹⁵ are R12-15-4, B ring is B-5 and X, X′, Y and Y′ are XY-17,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R¹², R¹³,R¹⁴ and R¹⁵ are R12-15-4, B ring is B-7 and X, X′, Y and Y′ are XY-6,

a compound wherein R⁴ and R⁵ are R45-3, R⁶ and R⁷ are R67-1, R¹², R¹³,R¹⁴ and R¹⁵ are R12-15-4, B ring is B-7 and X, X′, Y and Y′ are XY-17,

a compound wherein B ring is B-7, X and X′ are each independently —O—,NR¹— (wherein R¹ is hydrogen, lower alkyl, lower alkenyl or loweralkylcarbonyl) or —S(O)p- wherein p is an integer of 0-2,

Another embodiment of the present invention is

[4] a compounds of the formula (If′):

 

wherein one of B ring and C ring is optionally substituted 5- or6-membered heterocycle which contains one or two hetero atoms and theother is 6-membered heterocycle which contains at least one N atom,excluding a compound wherein every substituent of B ring is selectedfrom cyano and halogen,

X, X′, Y, X′ and W³ are the same as defined in [1] and W² is the same asdefined in [3],

R¹, taken together with Y or Y′, may form —(CH₂)m-, —(CH₂)₂—Q—(CH₂)₂—(wherein Q is CH₂, O, S or NR′), —CR′═CH—CH═CR′—, —CH═N—CH═CH—,—N═CH—N═CH—, —C(═O)—O(CH₂)n-, —C(═O)—NR′—(CH₂)n- or —C(═O)—NR′—N═CH—wherein m is 4 or 5, n is 2 or 3 and R′ is hydrogen, lower alkyl orlower alkenyl,

Y may be optionally substituted lower alkoxy when X is —CH₂—,

Y′ may be optionally substituted lower alkoxy when X′ is —CH₂—,

Y may be optionally substituted lower alkoxycarbonyl, optionallysubstituted lower alkylsulfonyl or optionally substituted arylsulfonylwhen X is —O— or —NR¹,

Y′ may be optionally substituted lower alkoxycarbonyl, optionallysubstituted lower alkylsulfonyl or optionally substituted arylsulfonylwhen X is —O— or NR¹—,

Y may be hydrogen or halogen when X is —CH₂— or NR¹—,

Y′ may be hydrogen or halogen when X is —CH₂— or —NR¹—,

R⁴, R⁵, R⁶ and R⁷ are the same as defined in [1],

salt or hydrate thereof. The following compounds among the compound(If′) are preferable.

a compound wherein B ring is B-2,

a compound wherein B ring is B-3,

a compound wherein B ring is B-4,

a compound wherein B ring is B-5,

a compound wherein B ring is B-6,

a compound wherein B ring is pyridine which may be substituted withlower alkyl or lower alkoxy,

a compound wherein C ring is C-1,

a compound wherein C ring is C-2,

a compound wherein C ring is optionally substituted morpholine ring,optionally substituted piperazine ring, optionally substituted imidazolering, optionally substituted triazole ring or optionally substitutedpyridine ring,

a compound wherein C ring is optionally substituted morpholine ring,optionally substituted piperazine ring, optionally substituted imidazolering, optionally substituted triazole ring or optionally substitutedpyridine ring (wherein the substituent is lower alkyl, aryl or loweralkenyloxy),

a compound wherein R⁴, R⁵, R⁶ and R⁷ are each independently hydrogen,hydroxy or lower alkylsulfonyloxy,

a compound wherein B ring is pyridine ring which may be substituted withlower alkyl or lower alkoxy, C ring is optionally substituted morpholinering, optionally substituted piperazine ring, optionally substitutedimidazole ring, optionally substituted triazole ring or optionallysubstituted pyridine ring (wherein the substituents are lower alkyl,aryl or lower alkenyloxy) and R⁴, R⁵, R⁶ and R⁷ are each independentlyhydrogen, hydroxy or lower alkylsulfonyloxy.

Another embodiment of the present invention is

[5] a compound of the formula (Ig′):

 

wherein A ring and C ring are each independently optionally substituted5- or 6-membered ring which contains one or two hetero atoms and W¹ is abond when A ring is 5-membered heterocycle,

X, X′ Y and Y′ are the same as defined in [1],

R¹, taken together with Y or Y′, may form —(CH₂)m—, —(CH₂)₂—Q—(CH₂)₂—(wherein Q is CH₂, O, S or NR′), —CR′═CH—CH═CR′—, —CH═N—CH═CH—,—N═CH—N═CH—, —C(═O)—O(CH₂)n—, —C(═O)—NR′—(CH₂)n— or C(═O)—NR′—N═CH—wherein m is 4 or 5, n is 2 or 3 and R′ is hydrogen, lower alkyl orlower alkenyl,

Y may be optionally substituted lower alkoxy when X is —CH₂—,

Y′ may be optionally substituted lower alkoxy when X′ is —CH₂—,

Y may be optionally substituted lower alkoxycarbonyl, optionallysubstituted lower alkylsulfonyl or optionally substituted arylsulfonylwhen X is —O— or NR¹,

Y′ may be optionally substituted lower alkoxycarbonyl, optionallysubstituted lower alkylsulfonyl or optionally substituted arylsulfonylwhen X′ is —O— or NR¹—,

Y may be hydrogen or halogen when X is —CH₂— or NR¹,

Y′ may be hydrogen or halogen when X′ is —CH₂— or NR¹—,

R⁸, R⁹, R¹⁰ and R¹¹ are the same as defined in [1] excluding a compoundwherein all of R⁸, R⁹, R¹⁰ and R¹¹ are selected from hydrogen andhalogen,

salt or hydrate thereof. The following compounds among the compound(Ig′) are preferable.

a compound wherein at least one of A ring and C ring is a 6-memberedring,

a compound wherein at least one of A ring and C ring is a 6-memberedring which contains N atom,

a compound wherein A ring is optionally substituted pyridine ring,

a compound wherein A ring is unsubstituted pyridine ring,

a compound wherein R⁸, R⁹, R¹⁰ and R¹¹ are each independently hydrogen,lower alkyl or lower alkoxy,

a compound wherein C ring is optionally substituted pyridine ring,optionally substituted pyrimidine ring or optionally substitutedpyrazine ring,

a compound wherein C ring is unsubstituted pyridine ring, unsubstitutedpyrimidine ring or unsubstituted pyrazine ring,

a compound wherein —X—Y is lower alkenyloxy or lower alkenylamino,

a compound wherein —X′—Y′ is amino which may be substituted with loweralkenyl,

a compound wherein A ring is unsubstituted pyridine ring, R⁸, R⁹, R¹⁰and R¹¹ are each independently hydrogen, lower alkyl or lower alkoxy, Cring is unsubstituted pyridine ring, unsubstituted pyrimidine ring orunsubstituted pyrazine ring, —X—Y is lower alkenyloxy or loweralkenylamino and —X′—Y′ is amino which may be substituted with loweralkenyl,

or salt or hydrate thereof.

Other preferable embodiments of the present invention are as follows.

[6] A pharmaceutical composition for use as an immunosuppressantcomprising the compound of the formula (Ib′):

 

wherein C ring and W³ are the same as defined in [1],

X and X′ are each independently —O—, —CH₂—, —NR¹— (wherein R¹ ishydrogen, optionally substituted lower alkyl, lower alkenyl, loweralkylcarbonyl or optionally substituted lower alkoxycarbonyl), —S(O)p—(wherein p is an integer of 0-2) or a bond,

Y and Y′ are the same as defined in [1],

R¹, taken together with Y or Y′, may form —(CH₂)m—, —(CH₂)—Q—(CH₂)₂—(wherein Q is CH₂, O, S or NR′), —CR′═CH—CH═CR′—, —CH═N—CH═CH—,—N═CH—N═CH—, —C(═O)—O(CH₂)n—, —C(═O)—NR′—(CH₂)n— or —C(═O)—NR′—N═CH—wherein m is 4 or 5, n is 2 or 3 and R′ is hydrogen, lower alkyl orlower alkenyl,

Y may be lower alkoxy when X is —CH₂—,

Y′ may be lower alkoxy when X′ is —CH₂—,

Y may be optionally substituted lower alkoxycarbonyl, optionallysubstituted lower alkylsulfonyl or optionally substituted arylsulfonylwhen X is —O— or NR¹—,

Y′ may be optionally substituted lower alkoxycarbonyl, optionallysubstituted lower alkylsulfonyl or optionally substituted arylsulfonylwhen X′ is —O— or —NR¹—,

Y may be hydrogen or halogen when X is —CH₂— or —NR¹—,

Y′ may be hydrogen or halogen when X′ is —CH₂— or NR¹,

Y′ may be hydrogen, hydroxy, halogen, nitro or oxo when X′ is a bond,R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰ and R¹¹ are the same as defined in [1],excluding a compound wherein all of R⁸, R⁹, R¹⁰ and R¹¹ are selectedfrom hydrogen and halogen,

salt or hydrate thereof,

[7] a pharmaceutical composition for use as an immunosuppressantcomprising the compound of the formula (Ia′):

 

wherein B ring is optionally substituted 5- or 6-membered heterocyclewhich contains one or two hetero atoms excluding a compound whereinevery substituent of B ring is selected from cyano and halogen,

W² is a bond when B ring is 5-membered heterocycle,

X, X′, Y and Y′ are the same as defined in [3],

R¹, taken together with Y or Y′, may form —(CH₂)m—, —(CH₂)₂—Q—(CH₂)₂—(wherein Q is CH₂, O, S or NR′), —CR′═CH—CH═CR′—, —CH═N—CH═CH—,—N═CH—N═CH—, —C(═O)—O(CH₂)n—, —C(═O)—NR′—(CH₂)n— or —C(═O)—NR′—N═CH—wherein m is 4 or 5, n is 2 or 3 and R′ is hydrogen, lower alkyl orlower alkenyl,

Y may be optionally substituted lower alkoxy when X is —CH₂—,

Y′ may be optionally substituted lower alkoxy when X′ is —CH₂—,

Y may be optionally substituted lower alkoxycarbonyl, optionallysubstituted lower alkylsulfonyl or optionally substituted arylsulfonylwhen X is —O— or NR¹—,

Y′ may be optionally substituted lower alkoxycarbonyl, optionallysubstituted lower alkylsulfonyl or optionally substituted arylsulfonylwhen X′ is —O— or NR¹—,

Y may be hydrogen or halogen when X is —CH₂— or —NR¹—,

Y′ may be hydrogen or halogen when.X′ is —CH₂— or NR¹,

R⁴, R⁵, R⁶, R⁷, R¹², R¹³, R¹⁴ and R¹⁵ are the same as defined in [3],excluding

(i) a compound wherein —X—Y and —X′—Y′ are simultaneously unsubstitutedlower alkyl, optionally substituted lower alkoxy or unsubstitutedacyloxy,

(ii) a compound wherein one of —X—Y and —X′—Y′ is methyl and the otheris methoxy, and

(iii) a compound wherein —X′—Y′ is hydrogen or halogen and —X—Y isunsubstituted lower alkyl, unsubstituted lower alkoxy ordi(lower)alkylamino,

salt or hydrate thereof,

[8] a pharmaceutical composition for use as an immunosuppressantcomprising the compound of the formula (If′), salt or hydrate thereofdescribed in [4],

[9] a pharmaceutical composition for use as an immunosuppressantcomprising the compound (Ig′), salt or hydrate thereof described in [5],

[10] a pharmaceutical composition for use as an antiallergic agentcomprising the compound of the formula (If′) described in [4], thecompound of the formula (Ig′) described in [5], the compound of theformula (Ib′) described in [6], the compound of the formula (Ia′)described in [7], salt, hydrate thereof,

[11] a pharmaceutical composition for use as a suppressant of the IgEproduction comprising the compound of the formula (If′) described in[4]the compound of the formula (Ig′) described in [5], the compound ofthe formula (Ib′) described in [6], the compound of the formula (Ia′)described in [7], salt, or hydrate thereof,

[12] Use of the compound of the formula (If′) described in [4], thecompound of the formula (Ig′) described in [5], the compound of theformula (Ib′) described in [6], the compound of the formula (Ia′)described in [7], salt, or hydrate thereof for manufacturing amedicament for suppressing an immune response, treating and/orpreventing allergic diseases,

[13] a method for suppressing an immune response or treating and/orpreventing allergic diseases comprising administering the compound ofthe formula (If′) described in [4], the compound of the formula (Ig′)described in [5]), the compound of the formula (Ib′) described in [6],the compound of the formula (Ia′) described in [7], salt, or hydratethereof and

[14] a method for treating and/or preventing allergic diseasescomprising administering the compound of the formula (If′) described in[4], the compound of the formula (Ig′) described in [5], the compound ofthe formula (Ib′) described in [6], the compound of the formula (Ia′)described in [7], salt, or hydrate thereof.

The preferable compounds of the present invention are the ones offollowing structures. The symbols A2, A5, . . . B1, B4, . . . T1, T2 . .. in the tables means as follows.

TABLE 1

R⁴ R⁵ R⁶ R⁷ X Y A2 H H H H O CH₂-2-furyl A5 H H H H O CH₂CH═CMe₂ A35 OMeH H H O CH₂CH═CMe₂ A37 F H H H O CH₂CH═CMe₂ A45 H H H H NH CH₂CH═CH2 A46H H H H NH CH₂CH═CMe₂ A49 H H H H NH CH₂-c-Hex A54 H H H H NHCH₂-2-furyl A66 H F H H NH iBu A67 H F H H NH CH₂CH═CMe₂ A68 H F H H NHcPent A69 H F H H NH cHex A70 H F H H NH CH₂cHex A76 H F H H N-iPrSO₂NHMe A77 H F H H NCH₂CH═CMe₂ SO₂NHMe A78 F H H H NH CH₂CH═CMe₂ A106 HF H H NH CH₂C₆H₅ A110 F H H H O CH₂C₆H₅

 

TABLE 2

R⁸ R⁹ R¹⁰ R¹¹ B1 OMe H H OMe B4 Me H H Me B7 Me Me Me Me B8 Me Me OMe MeB9 Me Me OH Me B10 Me Me Me OMe B12 OMe Me Me OMe B14 Me Me H Me B16 MeF H Me B17 OMe H H Me B24 Me Me Me COOMe B28 Me Me Me Cl B29 Me OMe H MeB30 COOMe Me Me Me B31 Cl Me Me Me B32 H Me Me Cl B33 Me H Cl Me B34 HMe Cl H B35 Me H H Cl B36 Me Me H H B37 H Me H Me B38 Me H Me H B39 OMeOMe H H B40 H OMe H OMe B41 OMe H OMe H B42 H Me H OMe B43 OMe H Me H

 

TABLE 3

R¹² R¹³ R¹⁴ R¹⁵

R¹² R¹³ R¹⁴ R¹⁵ T1-1 H H — H T2-4 H H Me — T2-1 H H H — T2-5 H NO₂ H —T2-2 Me H H — T5-1 H — H — T2-3 H Me H — T7-1 H H — —

 

TABLE 4

T1-1 B1 A2  T2-1 B1 A2  T1-1 B1 A5  T2-1 B1 A5  T1-1 B1 A35 T2-1 B1 A35T1-1 B1 A37 T2-1 B1 A37 T1-1 B1 A45 T2-1 B1 A45 T1-1 B1 A46 T2-1 B1 A46T1-1 B1 A49 T2-1 B1 A49 T1-1 B1 A54 T2-1 B1 A54 T1-1 B1 A66 T2-1 B1 A66T1-1 B1 A67 T2-1 B1 A67 T1-1 B1 A68 T2-1 B1 A68 T1-1 B1 A69 T2-1 B1 A69T1-1 B1 A70 T2-1 B1 A70 T1-1 B1 A76 T2-1 B1 A76 T1-1 B1 A77 T2-1 B1 A77T1-1 B1 A78 T2-1 B1 A78 T1-1 B1  A106 T2-1 B1  A106 T1-1 B1  A110 T2-1B1  A110 T2-2 B1 A2  T2-3 B1 A2  T2-2 B1 A5  T2-3 B1 A5  T2-2 B1 A35T2-3 B1 A35 T2-2 B1 A37 T2-3 B1 A37 T2-2 B1 A45 T2-3 B1 A45 T2-2 B1 A46T2-3 B1 A46 T2-2 B1 A49 T2-3 B1 A49 T2-2 B1 A54 T2-3 B1 A54 T2-2 B1 A66T2-3 B1 A66 T2-2 B1 A67 T2-3 B1 A67

 

TABLE 5 T2-2 B1 A68 T2-3 B1 A68 T2-2 B1 A69 T2-3 B1 A69 T2-2 B1 A70 T2-3B1 A70 T2-2 B1 A76 T2-3 B1 A76 T2-2 B1 A77 T2-3 B1 A77 T2-2 B1 A78 T2-3B1 A78 T2-2 B1 A106 T2-3 B1 A106 T2-2 B1 A110 T2-3 B1 A110 T2-4 B1 A2T2-5 B1 A2 T2-4 B1 A5 T2-5 B1 A5 T2-4 B1 A35 T2-5 B1 A35 T2-4 B1 A37T2-5 B1 A37 T2-4 B1 A45 T2-5 B1 A45 T2-4 B1 A46 T2-5 B1 A46 T2-4 B1 A49T2-5 B1 A49 T2-4 B1 A54 T2-5 B1 A54 T2-4 B1 A66 T2-5 B1 A66 T2-4 B1 A67T2-5 B1 A67 T2-4 B1 A68 T2-5 B1 A68 T2-4 B1 A69 T2-5 B1 A69 T2-4 B1 A70T2-5 B1 A70 T2-4 B1 A76 T2-5 B1 A76 T2-4 B1 A77 T2-5 B1 A77 T2-4 B1 A78T2-5 B1 A78 T2-4 B1 A106 T2-5 B1 A106 T2-4 B1 A110 T2-5 B1 A110 T5-1 B1A2 T7-1 B1 A2 T5-1 B1 A5 T7-1 B1 A5 T5-1 B1 A35 T7-1 B1 A35 T5-1 B1 A37T7-1 B1 A37 T5-1 B1 A45 T7-1 B1 A45 T5-1 B1 A46 T7-1 B1 A46 T5-1 B1 A49T7-1 B1 A49 T5-1 B1 A54 T7-1 B1 A54 T5-1 B1 A66 T7-1 B1 A66 T5-1 B1 A67T7-1 B1 A67 T5-1 B1 A68 T7-1 B1 A68 T5-1 B1 A69 T7-1 B1 A69 T5-1 B1 A70T7-1 B1 A70 T5-1 B1 A76 T7-1 B1 A76 T5-1 B1 A77 T7-1 B1 A77 T5-1 B1 A78T7-1 B1 A78 T5-1 B1 A106 T7-1 B1 A106 T5-1 B1 A110 T7-1 B1 A110

 

TABLE 6 T1-1 B4 A2 T2-1 B4 A2 T1-1 B4 A5 T2-1 B4 A5 T1-1 B4 A35 T2-1 B4A35 T1-1 B4 A37 T2-1 B4 A37 T1-1 B4 A45 T2-1 B4 A45 T1-1 B4 A46 T2-1 B4A46 T1-1 B4 A49 T2-1 B4 A49 T1-1 B4 A54 T2-1 B4 A54 T1-1 B4 A66 T2-1 B4A66 TI-1 B4 A67 T2-1 B4 A67 T1-1 B4 A68 T2-1 B4 A68 T1-1 B4 A69 T2-1 B4A69 T1-1 B4 A70 T2-1 B4 A70 T1-1 B4 A76 T2-1 B4 A76 T1-1 B4 A77 T2-1 B4A77 T1-1 B4 A78 T2-1 B4 A78 T1-1 B4 A106 T2-1 B4 A106 T1-1 B4 A110 T2-1B4 A110 T2-2 B4 A2 T2-3 B4 A2 T2-2 B4 A5 T2-3 B4 A5 T2-2 B4 A35 T2-3 B4A35 T2-2 B4 A37 T2-3 B4 A37 T2-2 B4 A45 T2-3 B4 A45 T2-2 B4 A46 T2-3 B4A46 T2-2 B4 A49 T2-3 B4 A49 T2-2 B4 A54 T2-3 B4 A54 T2-2 B4 A66 T2-3 B4A66 T2-2 B4 A67 T2-3 B4 A67 T2-2 B4 A68 T2-3 B4 A68 T2-2 B4 A69 T2-3 B4A69 T2-2 B4 A70 T2-3 B4 A70 T2-2 B4 A76 T2-3 B4 A76 T2-2 B4 A77 T2-3 B4A77 T2-2 B4 A78 T2-3 B4 A78 T2-2 B4 A106 T2-3 B4 A106 T2-2 B4 A110 T2-3B4 A110 T2-4 B4 A2 T2-5 B4 A2 T2-4 B4 A5 T2-5 B4 A5 T2-4 B4 A35 T2-5 B4A35 T2-4 B4 A37 T2-5 B4 A37 T2-4 B4 A45 T2-5 B4 A45 T2-4 B4 A46 T2-5 B4A46 T2-4 B4 A49 T2-5 B4 A49 T2-4 B4 A54 T2-5 B4 A54

 

TABLE 7 T2-4 B4 A66 T2-5 B4 A66 T2-4 B4 A67 T2-5 B4 A67 T2-4 B4 A68 T2-5B4 A68 T2-4 B4 A69 T2-5 B4 A69 T2-4 B4 A70 T2-5 B4 A70 T2-4 B4 A76 T2-5B4 A76 T2-4 B4 A77 T2-5 B4 A77 T2-4 B4 A78 T2-5 B4 A78 T2-4 B4 A106 T2-5B4 A106 T2-4 B4 A110 T2-5 B4 A110 T5-1 B4 A2 T7-1 B4 A2 T5-1 B4 A5 T7-1B4 A5 T5-1 B4 A35 T7-1 B4 A35 T5-1 B4 A37 T7-1 B4 A37 T5-1 B4 A45 T7-1B4 A45 T5-1 B4 A46 T7-1 B4 A46 T5-1 B4 A49 T7-1 B4 A49 T5-1 B4 A54 T7-1B4 A54 T5-1 B4 A66 T7-1 B4 A66 T5-1 B4 A67 T7-1 B4 A67 T5-1 B4 A68 T7-1B4 A68 T5-1 B4 A69 T7-1 B4 A69 T5-1 B4 A70 T7-1 B4 A70 T5-1 B4 A76 T7-1B4 A76 T5-1 B4 A77 T7-1 B4 A77 T5-1 B4 A78 T7-1 B4 A78 T5-1 B4 A106 T7-1B4 A106 T5-1 B4 A110 T7-1 B4 A110 T1-1 B7 A2 T2-1 B7 A2 T1-1 B7 A5 T2-1B7 A5 T1-1 B7 A35 T2-1 B7 A35 T1-1 B7 A37 T2-1 B7 A37 T1-1 B7 A45 T2-1B7 A45 T1-1 B7 A46 T2-1 B7 A46 T1-1 B7 A49 T2-1 B7 A49 T1-1 B7 A54 T2-1B7 A54 T1-1 B7 A66 T2-1 B7 A66 T1-1 B7 A67 T2-1 B7 A67 T1-1 B7 A68 T2-1B7 A68 T1-1 B7 A69 T2-1 B7 A69 T1-1 B7 A70 T2-1 B7 A70 T1-1 B7 A76 T2-1B7 A76 T1-1 B7 A77 T2-1 B7 A77 T1-1 B7 A78 T2-1 B7 A78

 

TABLE 8 T1-1 B7 A106 T2-1 B7 A106 T1-1 B7 A110 T2-1 B7 A110 T2-2 B7 A2T2-3 B7 A2 T2-2 B7 A5 T2-3 B7 A5 T2-2 B7 A35 T2-3 B7 A35 T2-2 B7 A37T2-3 B7 A37 T2-2 B7 A45 T2-3 B7 A45 T2-2 B7 A46 T2-3 B7 A46 T2-2 B7 A49T2-3 B7 A49 T2-2 B7 A54 T2-3 B7 A54 T2-2 B7 A66 T2-3 B7 A66 T2-2 B7 A67T2-3 B7 A67 T2-2 B7 A68 T2-3 B7 A68 T2-2 B7 A69 T2-3 B7 A69 T2-2 B7 A76T2-3 B7 A70 T2-2 B7 A76 T2-3 B7 A76 T2-2 B7 A77 T2-3 B7 A77 T2-2 B7 A78T2-3 B7 A78 T2-2 B7 A106 T2-3 B7 A106 T2-2 B7 A110 T2-3 B7 A110 T2-4 B7A2 T2-5 B7 A2 T2-4 B7 A5 T2-5 B7 A5 T2-4 B7 A35 T2-5 B7 A35 T2-4 B7 A37T2-5 B7 A37 T2-4 B7 A45 T2-5 B7 A45 T2-4 B7 A46 T2-5 B7 A46 T2-4 B7 A49T2-5 B7 A49 T2-4 B7 A54 T2-5 B7 A54 T2-4 B7 A66 T2-5 B7 A66 T2-4 B7 A67T2-5 B7 A67 T2-4 B7 A68 T2-5 B7 A68 T2-4 B7 A69 T2-5 B7 A69 T2-4 B7 A70T2-5 B7 A70 T2-4 B7 A76 T2-5 B7 A76 T2-4 B7 A77 T2-5 B7 A77 T2-4 B7 A78T2-5 B7 A78 T2-4 B7 A106 T2-5 B7 A106 T2-4 B7 A110 T2-5 B7 A110 T5-1 B7A2 T7-1 B7 A2 T5-1 B7 A5 T7-1 B7 A5 T5-1 B7 A35 T7-1 B7 A35 T5-1 B7 A37T7-1 B7 A37 T5-1 B7 A45 T7-1 B7 A45

 

TABLE 9 T5-1 B7 A46 T7-1 B7 A46 T5-1 B7 A49 T7-1 B7 A49 T5-1 B7 A54 T7-1B7 A54 T5-1 B7 A66 T7-1 B7 A66 T5-1 B7 A67 T7-1 B7 A67 T5-1 B7 A68 T7-1B7 A68 T5-1 B7 A69 T7-1 B7 A69 T5-1 B7 A70 T7-1 B7 A70 T5-1 B7 A76 T7-1B7 A76 T5-1 B7 A77 T7-1 B7 A77 T5-1 B7 A78 T7-1 B7 A78 T5-1 B7 A106 T7-1B7 A106 T5-1 B7 A110 T7-1 B7 A110 T1-1 B8 A2 T2-1 B8 A2 T1-1 B8 A5 T2-1B8 A5 T1-1 B8 A35 T2-1 B8 A35 T1-1 B8 A37 T2-1 B8 A37 T1-1 B8 A45 T2-1B8 A45 T1-1 B8 A46 T2-1 B8 A46 T1-1 B8 A49 T2-1 B8 A49 T1-1 B8 A54 T2-1B8 A54 T1-1 B8 A66 T2-1 B8 A66 T1-1 B8 A67 T2-1 B8 A67 T1-1 B8 A68 T2-1B8 A68 T1-1 B8 A69 T2-1 B8 A69 T1-1 B8 A70 T2-1 B8 A70 T1-1 B8 A76 T2-1B8 A76 T1-1 B8 A77 T2-1 B8 A77 T1-1 B8 A78 T2-1 B8 A78 T1-1 B8 A106 T2-1B8 A106 T1-1 B8 A110 T2-1 B8 A110 T2-2 B8 A2 T2-3 B8 A2 T2-2 B8 A5 T2-3B8 A5 T2-2 B8 A35 T2-3 B8 A35 T2-2 B8 A37 T2-3 B8 A37 T2-2 B8 A45 T2-3B8 A45 T2-2 B8 A46 T2-3 B8 A46 T2-2 B8 A49 T2-3 B8 A49 T2-2 B8 A54 T2-3B8 A54 T2-2 B8 A66 T2-3 B8 A66 T2-2 B8 A67 T2-3 B8 A67 T2-2 B8 A68 T2-3B8 A68 T2-2 B8 A69 T2-3 B8 A69

 

TABLE 10 T2-2 B8 A70 T2-3 B8 A70 T2-2 B8 A76 T2-3 B8 A76 T2-2 B8 A77T2-3 B8 A77 T2-2 B8 A78 T2-3 B8 A78 T2-2 B8 A106 T2-3 B8 A106 T2-2 B8A110 T2-3 B8 A110 T2-4 B8 A2 T2-5 B8 A2 T2-4 B8 A5 T2-5 B8 A5 T2-4 B8A35 T2-5 B8 A35 T2-4 B8 A37 T2-5 B8 A37 T2-4 B8 A45 T2-5 B8 A45 T2-4 B8A46 T2-5 B8 A46 T2-4 B8 A49 T2-5 B8 A49 T2-4 B8 A54 T2-5 B8 A54 T2-4 B8A66 T2-5 B8 A66 T2-4 B8 A67 T2-5 B8 A67 T2-4 B8 A68 T2-5 B8 A68 T2-4 B8A69 T2-5 B8 A69 T2-4 B8 A70 T2-5 B8 A70 T2-4 B8 A76 T2-5 B8 A76 T2-4 B8A77 T2-5 B8 A77 T2-4 B8 A78 T2-5 B8 A78 T2-4 B8 A106 T2-5 B8 A106 T2-4B8 A110 T2-5 B8 A110 T5-1 B8 A2 T7-1 B8 A2 T5-1 B8 A5 T7-1 B8 A5 T5-1 B8A35 T7-1 B8 A35 T5-1 B8 A37 T7-1 B8 A37 T5-1 B8 A45 T7-1 B8 A45 T5-1 B8A46 T7-1 B8 A46 T5-1 B8 A49 T7-1 B8 A49 T5-1 B8 A54 T7-1 B8 A54 T5-1 B8A66 T7-1 B8 A66 T5-1 B8 A67 T7-1 B8 A67 T5-1 B8 A68 T7-1 B8 A68 T5-1 B8A69 T7-1 B8 A69 T5-1 B8 A76 T7-1 B8 A70 T5-1 B8 A76 T7-1 B8 A76 T5-1 B8A77 T7-1 B8 A77 T5-1 B8 A78 T7-1 B8 A78 T5-1 B8 A106 T7-1 B8 A106 T5-1B8 A110 T7-1 B8 A110 T1-1 B9 A2 T2-1 B9 A2

 

TABLE 11 T1-1 B9 A5 T2-1 B9 A5 T1-1 B9 A35 T2-1 B9 A35 T1-1 B9 A37 T2-1B9 A37 T1-1 B9 A45 T2-1 B9 A45 T1-1 B9 A46 T2-1 B9 A46 T1-1 B9 A49 T2-1B9 A49 T1-1 B9 A54 T2-1 B9 A54 T1-1 B9 A66 T2-1 B9 A66 T1-1 B9 A67 T2-1B9 A67 T1-1 B9 A68 T2-1 B9 A68 T1-1 B9 A69 T2-1 B9 A69 T1-1 B9 A70 T2-1B9 A70 T1-1 B9 A76 T2-1 B9 A76 T1-1 B9 A77 T2-1 B9 A77 T1-1 B9 A78 T2-1B9 A78 T1-1 B9 A106 T2-1 B9 A106 T1-1 B9 A110 T2-1 B9 A110 T2-2 B9 A2T2-3 B9 A2 T2-2 B9 A5 T2-3 B9 A5 T2-2 B9 A35 T2-3 B9 A35 T2-2 B9 A37T2-3 B9 A37 T2-2 B9 A45 T2-3 B9 A45 T2-2 B9 A46 T2-3 B9 A46 T2-2 B9 A49T2-3 B9 A49 T2-2 B9 A54 T2-3 B9 A54 T2-2 B9 A66 T2-3 B9 A66 T2-2 B9 A67T2-3 B9 A67 T2-2 B9 A68 T2-3 B9 A68 T2-2 B9 A69 T2-3 B9 A69 T2-2 B9 A70T2-3 B9 A70 T2-2 B9 A76 T2-3 B9 A76 T2-2 B9 A77 T2-3 B9 A77 T2-2 B9 A78T2-3 B9 A78 T2-2 B9 A106 T2-3 B9 A106 T2-2 B9 A110 T2-3 B9 A110 T2-4 B9A2 T2-5 B9 A2 T2-4 B9 A5 T2-5 B9 A5 T2-4 B9 A35 T2-5 B9 A35 T2-4 B9 A37T2-5 B9 A37 T2-4 B9 A45 T2-5 B9 A45 T2-4 B9 A46 T2-5 B9 A46 T2-4 B9 A49T2-5 B9 A49 T2-4 B9 A54 T2-5 B9 A54

 

TABLE 12 T2-4 B9 A66 T2-5 B9 A66 T2-4 B9 A67 T2-5 B9 A67 T2-4 B9 A68T2-5 B9 A68 T2-4 B9 A69 T2-5 B9 A69 T2-4 B9 A70 T2-5 B9 A70 T2-4 B9 A76T2-5 B9 A76 T2-4 B9 A77 T2-5 B9 A77 T2-4 B9 A78 T2-5 B9 A78 T2-4 B9 A106T2-5 B9 A106 T2-4 B9 A110 T2-5 B9 A110 T5-1 B9 A2 T7-1 B9 A2 T5-1 B9 A5T7-1 B9 A5 T5-1 B9 A35 T7-1 B9 A35 T5-1 B9 A37 T7-1 B9 A37 T5-1 B9 A45T7-1 B9 A45 T5-1 B9 A46 T7-1 B9 A46 T5-1 B9 A49 T7-1 B9 A49 T5-1 B9 A54T7-1 B9 A54 T5-1 B9 A66 T7-1 B9 A66 T5-1 B9 A67 T7-1 B9 A67 T5-1 B9 A68T7-1 B9 A68 T5-1 B9 A69 T7-1 B9 A69 T5-1 B9 A70 T7-1 B9 A70 T5-1 B9 A76T7-1 B9 A76 T5-1 B9 A77 T7-1 B9 A77 T5-1 B9 A78 T7-1 B9 A78 T5-1 B9 A106T7-1 B9 A106 T5-1 B9 A110 T7-1 B9 A110 T1-1 B10 A2 T2-1 B10 A2 T1-1 B10A5 T2-1 B10 A5 T1-1 B10 A35 T2-1 B10 A35 T1-1 B10 A37 T2-1 B10 A37 T1-1B10 A45 T2-1 B10 A45 T1-1 B10 A46 T2-1 B10 A46 T1-1 B10 A49 T2-1 B10 A49T1-1 B10 A54 T2-1 B10 A54 T1-1 B10 A66 T2-1 B10 A66 T1-1 B10 A67 T2-1B10 A67 T1-1 B10 A68 T2-1 B10 A68 T1-1 B10 A69 T2-1 B10 A69 T1-1 B10 A70T2-1 B10 A70 T1-1 B10 A76 T2-1 B10 A76 T1-1 B10 A77 T2-1 B10 A77 T1-1B10 A78 T2-1 B10 A78

 

TABLE 13 T1-1 B10 A106 T2-1 B10 A106 T1-1 B10 A110 T2-1 B10 A110 T2-2B10 A2 T2-3 B10 A2 T2-2 B10 A5 T2-3 B10 A5 T2-2 B10 A35 T2-3 B10 A35T2-2 B10 A37 T2-3 B10 A37 T2-2 B10 A45 T2-3 B10 A45 T2-2 B10 A46 T2-3B10 A46 T2-2 B10 A49 T2-3 B10 A49 T2-2 B10 A54 T2-3 B10 A54 T2-2 B10 A66T2-3 B10 A66 T2-2 B10 A67 T2-3 B10 A67 T2-2 B10 A68 T2-3 B10 A68 T2-2B10 A69 T2-3 B10 A69 T2-2 B10 A70 T2-3 B10 A70 T2-2 B10 A76 T2-3 B10 A76T2-2 B10 A77 T2-3 B10 A77 T2-2 B10 A78 T2-3 B10 A78 T2-2 B10 A106 T2-3B10 A106 T2-2 B10 A110 T2-3 B10 A110 T2-4 B10 A2 T2-5 B10 A2 T2-4 B10 A5T2-5 B10 A5 T2-4 B10 A35 T2-5 B10 A35 T2-4 B10 A37 T2-5 B10 A37 T2-4 B10A45 T2-5 B10 A45 T2-4 B10 A46 T2-5 B10 A46 T2-4 B10 A49 T2-5 B10 A49T2-4 B10 A54 T2-5 B10 A54 T2-4 B10 A66 T2-5 B10 A66 T2-4 B10 A67 T2-5B10 A67 T2-4 B10 A68 T2-5 B10 A68 T2-4 B10 A69 T2-5 B10 A69 T2-4 B10 A70T2-5 B10 A70 T2-4 B10 A76 T2-5 B10 A76 T2-4 B10 A77 T2-5 B10 A77 T2-4B10 A78 T2-5 B10 A78 T2-4 B10 A106 T2-5 B10 A106 T2-4 B10 A110 T2-5 B10A110 T5-1 B10 A2 T7-1 B10 A2 T5-1 B10 A5 T7-1 B10 A5 T5-1 B10 A35 T7-1B10 A35 T5-1 B10 A37 T7-1 B10 A37 T5-1 B10 A45 T7-1 B10 A45

 

TABLE 14 T5-1 B10 A46 T7-1 B10 A46 T5-1 B10 A49 T7-1 B10 A49 T5-1 B10A54 T7-1 B10 A54 T5-1 B10 A66 T7-1 B10 A66 T5-1 B10 A67 T7-1 B10 A67T5-1 B10 A68 T7-1 B10 A68 T5-1 B10 A69 T7-1 B10 A69 T5-1 B10 A70 T7-1B10 A70 T5-1 B10 A76 T7-1 B10 A76 T5-1 B10 A77 T7-1 B10 A77 T5-1 B10 A78T7-1 B10 A78 T5-1 B10 A106 T7-1 B10 A106 T5-1 B10 A110 T7-1 B10 A110T1-1 B12 A2 T2-1 B12 A2 T1-1 B12 A5 T2-1 B12 A5 T1-1 B12 A35 T2-1 B12A35 T1-1 B12 A37 T2-1 B12 A37 T1-1 B12 A45 T2-1 B12 A45 T1-1 B12 A46T2-1 B12 A46 T1-1 B12 A49 T2-1 B12 A49 T1-1 B12 A54 T2-1 B12 A54 T1-1B12 A66 T2-1 B12 A66 T1-1 B12 A67 T2-1 B12 A67 T1-1 B12 A68 T2-1 B12 A68T1-1 B12 A69 T2-1 B12 A69 T1-1 B12 A70 T2-1 B12 A70 T1-1 B12 A76 T2-1B12 A76 T1-1 B12 A77 T2-1 B12 A77 T1-1 B12 A78 T2-1 B12 A78 T1-1 B12A106 T2-1 B12 A106 T1-1 B12 A110 T2-1 B12 A110 T2-2 B12 A2 T2-3 B12 A2T2-2 B12 A5 T2-3 B12 A5 T2-2 B12 A35 T2-3 B12 A35 T2-2 B12 A37 T2-3 B12A37 T2-2 B12 A45 T2-3 B12 A45 T2-2 B12 A46 T2-3 B12 A46 T2-2 B12 A49T2-3 B12 A49 T2-2 B12 A54 T2-3 B12 A54 T2-2 B12 A66 T2-3 B12 A66 T2-2B12 A67 T2-3 B12 A67 T2-2 B12 A68 T2-3 B12 A68 T2-2 B12 A69 T2-3 B12 A69

 

TABLE 15 T2-2 B12 A70 T2-3 B12 A70 T2-2 B12 A76 T2-3 B12 A76 T2-2 B12A77 T2-3 B12 A77 T2-2 B12 A78 T2-3 B12 A78 T2-2 B12 A106 T2-3 B12 A106T2-2 B12 A110 T2-3 B12 A110 T2-4 B12 A2 T2-5 B12 A2 T2-4 B12 A5 T2-5 B12A5 T2-4 B12 A35 T2-5 B12 A35 T2-4 B12 A37 T2-5 B12 A37 T2-4 B12 A45 T2-5B12 A45 T2-4 B12 A46 T2-5 B12 A46 T2-4 B12 A49 T2-5 B12 A49 T2-4 B12 A54T2-5 B12 A54 T2-4 B12 A66 T2-5 B12 A66 T2-4 B12 A67 T2-5 B12 A67 T2-4B12 A68 T2-5 B12 A68 T2-4 B12 A69 T2-5 B12 A69 T2-4 B12 A70 T2-5 B12 A70T2-4 B12 A76 T2-5 B12 A76 T2-4 B12 A77 T2-5 B12 A77 T2-4 B12 A78 T2-5B12 A78 T2-4 B12 A106 T2-5 B12 A106 T2-4 B12 A110 T2-5 B12 A110 T5-1 B12A2 T7-1 B12 A2 T5-1 B12 A5 T7-1 B12 A5 T5-1 B12 A35 T7-1 B12 A35 T5-1B12 A37 T7-1 B12 A37 T5-1 B12 A45 T7-1 B12 A45 T5-1 B12 A46 T7-1 B12 A46T5-1 B12 A49 T7-1 B12 A49 T5-1 B12 A54 T7-1 B12 A54 T5-1 B12 A66 T7-1B12 A66 T5-1 B12 A67 T7-1 B12 A67 T5-1 B12 A68 T7-1 B12 A68 T5-1 B12 A69T7-1 B12 A69 T5-1 B12 A70 T7-1 B12 A70 T5-1 B12 A76 T7-1 B12 A76 T5-1B12 A77 T7-1 B12 A77 T5-1 B12 A78 T7-1 B12 A78 T5-1 B12 A106 T7-1 B12A106 T5-1 B12 A110 T7-1 B12 A110 T1-1 B14 A2 T2-1 B14 A2

 

TABLE 16 T1-1 B14 A5 T2-1 B14 A5 T1-1 B14 A35 T2-1 B14 A35 T1-1 B14 A37T2-1 B14 A37 T1-1 B14 A45 T2-1 B14 A45 T1-1 B14 A46 T2-1 B14 A46 T1-1B14 A49 T2-1 B14 A49 T1-1 B14 A54 T2-1 B14 A54 T1-1 B14 A66 T2-1 B14 A66T1-1 B14 A67 T2-1 B14 A67 T1-1 B14 A68 T2-1 B14 A68 T1-1 B14 A69 T2-1B14 A69 T1-1 B14 A70 T2-1 B14 A70 T1-1 B14 A76 T2-1 B14 A76 T1-1 B14 A77T2-1 B14 A77 T1-1 B14 A78 T2-1 B14 A78 T1-1 B14 A106 T2-1 B14 A106 T1-1B14 A110 T2-1 B14 A110 T2-2 B14 A2 T2-3 B14 A2 T2-2 B14 A5 T2-3 B14 A5T2-2 B14 A35 T2-3 B14 A35 T2-2 B14 A37 T2-3 B14 A37 T2-2 B14 A45 T2-3B14 A45 T2-2 B14 A46 T2-3 B14 A46 T2-2 B14 A49 T2-3 B14 A49 T2-2 B14 A54T2-3 B14 A54 T2-2 B14 A66 T2-3 B14 A66 T2-2 B14 A67 T2-3 B14 A67 T2-2B14 A68 T2-3 B14 A68 T2-2 B14 A69 T2-3 B14 A69 T2-2 B14 A70 T2-3 B14 A70T2-2 B14 A76 T2-3 B14 A76 T2-2 B14 A77 T2-3 B14 A77 T2-2 B14 A78 T2-3B14 A78 T2-2 B14 A106 T2-3 B14 A106 T2-2 B14 A110 T2-3 B14 A110 T2-4 B14A2 T2-5 B14 A2 T2-4 B14 A5 T2-5 B14 A5 T2-4 B14 A35 T2-5 B14 A35 T2-4B14 A37 T2-5 B14 A37 T2-4 B14 A45 T2-5 B14 A45 T2-4 B14 A46 T2-5 B14 A46T2-4 B14 A49 T2-5 B14 A49 T2-4 B14 A54 T2-5 B14 A54

 

TABLE 17 T2-4 B14 A66 T2-5 B14 A66 T2-4 B14 A67 T2-5 B14 A67 T2-4 B14A68 T2-5 B14 A68 T2-4 B14 A69 T2-5 B14 A69 T2-4 B14 A70 T2-5 B14 A70T2-4 B14 A76 T2-5 B14 A76 T2-4 B14 A77 T2-5 B14 A77 T2-4 B14 A78 T2-5B14 A78 T2-4 B14 A106 T2-5 B14 A106 T2-4 B14 A110 T2-5 B14 A110 T5-1 B14A2 T7-1 B14 A2 T5-1 B14 A5 T7-1 B14 A5 T5-1 B14 A35 T7-1 B14 A35 T5-1B14 A37 T7-1 B14 A37 T5-1 B14 A45 T7-1 B14 A45 T5-1 B14 A46 T7-1 B14 A46T5-1 B14 A49 T7-1 B14 A49 T5-1 B14 A54 T7-1 B14 A54 T5-1 B14 A66 T7-1B14 A66 T5-1 B14 A67 T7-1 B14 A67 T5-1 B14 A68 T7-1 B14 A68 T5-1 B14 A69T7-1 B14 A69 T5-1 B14 A70 T7-1 B14 A70 T5-1 B14 A76 T7-1 B14 A76 T5-1B14 A77 T7-1 B14 A77 T5-1 B14 A78 T7-1 B14 A78 T5-1 B14 A106 T7-1 B14A106 T5-1 B14 A110 T7-1 B14 A110 T1-1 B16 A2 T2-1 B16 A2 T1-1 B16 A5T2-1 B16 A5 T1-1 B16 A35 T2-1 B16 A35 T1-1 B16 A37 T2-1 B16 A37 T1-1 B16A45 T2-1 B16 A45 T1-1 B16 A46 T2-1 B16 A46 T1-1 B16 A49 T2-1 B16 A49T1-1 B16 A54 T2-1 B16 A54 T1-1 B16 A66 T2-1 B16 A66 T1-1 B16 A67 T2-1B16 A67 T1-1 B16 A68 T2-1 B16 A68 T1-1 B16 A69 T2-1 B16 A69 T1-1 B16 A70T2-1 B16 A70 T1-1 B16 A76 T2-1 B16 A76 T1-1 B16 A77 T2-1 B16 A77

 

TABLE 18 T1-1 B16 A78 T2-1 B16 A78 T1-1 B16 A106 T2-1 B16 A106 T1-1 B16A110 T2-1 B16 A110 T2-2 B16 A2 T2-3 B16 A2 T2-2 B16 A5 T2-3 B16 A5 T2-2B16 A35 T2-3 B16 A35 T2-2 B16 A37 T2-3 B16 A37 T2-2 B16 A45 T2-3 B16 A45T2-2 B16 A46 T2-3 B16 A46 T2-2 B16 A49 T2-3 B16 A49 T2-2 B16 A54 T2-3B16 A54 T2-2 B16 A66 T2-3 B16 A66 T2-2 B16 A67 T2-3 B16 A67 T2-2 B16 A68T2-3 B16 A68 T2-2 B16 A69 T2-3 B16 A69 T2-2 B16 A70 T2-3 B16 A70 T2-2B16 A76 T2-3 B16 A76 T2-2 B16 A77 T2-3 B16 A77 T2-2 B16 A78 T2-3 B16 A78T2-2 B16 A106 T2-3 B16 A106 T2-2 B16 A110 T2-3 B16 A110 T2-4 B16 A2 T2-5B16 A2 T2-4 B16 A5 T2-5 B16 A5 T2-4 B16 A35 T2-5 B16 A35 T2-4 B16 A37T2-5 B16 A37 T2-4 B16 A45 T2-5 B16 A45 T2-4 B16 A46 T2-5 B16 A46 T2-4B16 A49 T2-5 B16 A49 T2-4 B16 A54 T2-5 B16 A54 T2-4 B16 A66 T2-5 B16 A66T2-4 B16 A67 T2-5 B16 A67 T2-4 B16 A68 T2-5 B16 A68 T2-4 B16 A69 T2-5B16 A69 T2-4 B16 A70 T2-5 B16 A70 T2-4 B16 A76 T2-5 B16 A76 T2-4 B16 A77T2-5 B16 A77 T2-4 B16 A78 T2-5 B16 A78 T2-4 B16 A106 T2-5 B16 A106 T2-4B16 A110 T2-5 B16 A110 T5-1 B16 A2 T7-1 B16 A2 T5-1 B16 A5 T7-1 B16 A5T5-1 B16 A35 T7-1 B16 A35 T5-1 B16 A37 T7-1 B16 A37

 

TABLE 19 T5-1 B16 A45 T7-1 B16 A45 T5-1 B16 A46 T7-1 B16 A46 T5-1 B16A49 T7-1 B16 A49 T5-1 B16 A54 T7-1 B16 A54 T5-1 B16 A66 T7-1 B16 A66T5-1 B16 A67 T7-1 B16 A67 T5-1 B16 A68 T7-1 B16 A68 T5-1 B16 A69 T7-1B16 A69 T5-1 B16 A70 T7-1 B16 A70 T5-1 B16 A76 T7-1 B16 A76 T5-1 B16 A77T7-1 B16 A77 T5-1 B16 A78 T7-1 B16 A78 T5-1 B16 A106 T7-1 B16 A106 T5-1B16 A110 T7-1 B16 A110 T1-1 B17 A2 T2-1 B17 A2 T1-1 B17 A5 T2-1 B17 A5T1-1 B17 A35 T2-1 B17 A35 T1-1 B17 A37 T2-1 B17 A37 T1-1 B17 A45 T2-1B17 A45 T1-1 B17 A46 T2-1 B17 A46 T1-1 B17 A49 T2-1 B17 A49 T1-1 B17 A54T2-1 B17 A54 T1-1 B17 A66 T2-1 B17 A66 T1-1 B17 A67 T2-1 B17 A67 T1-1B17 A68 T2-1 B17 A68 T1-1 B17 A69 T2-1 B17 A69 T1-1 B17 A70 T2-1 B17 A70T1-1 B17 A76 T2-1 B17 A76 T1-1 B17 A77 T2-1 B17 A77 T1-1 B17 A78 T2-1B17 A78 T1-1 B17 A106 T2-1 B17 A106 T1-1 B17 A110 T2-1 B17 A110 T2-2 B17A2 T2-3 B17 A2 T2-2 B17 A5 T2-3 B17 A5 T2-2 B17 A35 T2-3 B17 A35 T2-2B17 A37 T2-3 B17 A37 T2-2 B17 A45 T2-3 B17 A45 T2-2 B17 A46 T2-3 B17 A46T2-2 B17 A49 T2-3 B17 A49 T2-2 B17 A54 T2-3 B17 A54 T2-2 B17 A66 T2-3B17 A66 T2-2 B17 A67 T2-3 B17 A67 T2-2 B17 A68 T2-3 B17 A68

 

TABLE 20 T2-2 B17 A69 T2-3 B17 A69 T2-2 B17 A70 T2-3 B17 A70 T2-2 B17A76 T2-3 B17 A76 T2-2 B17 A77 T2-3 B17 A77 T2-2 B17 A78 T2-3 B17 A78T2-2 B17  A106 T2-3 B17  A106 T2-2 B17  A110 T2-3 B17  A110 T2-4 B17 A2 T2-5 B17 A2  T2-4 B17 A5  T2-5 B17 A5  T2-4 B17 A35 T2-5 B17 A35 T2-4B17 A37 T2-5 B17 A37 T2-4 B17 A45 T2-5 B17 A45 T2-4 B17 A46 T2-5 B17 A46T2-4 B17 A49 T2-5 B17 A49 T2-4 B17 A54 T2-5 B17 A54 T2-4 B17 A66 T2-5B17 A66 T2-4 B17 A67 T2-5 B17 A67 T2-4 B17 A68 T2-5 B17 A68 T2-4 B17 A69T2-5 B17 A69 T2-4 B17 A70 T2-5 B17 A70 T2-4 B17 A76 T2-5 B17 A76 T2-4B17 A77 T2-5 B17 A77 T2-4 B17 A78 T2-5 B17 A78 T2-4 B17  A106 T2-5 B17 A106 T2-4 B17  A110 T2-5 B17  A110 T5-1 B17 A2  T7-1 B17 A2  T5-1 B17A5  T7-1 B17 A5  T5-1 B17 A35 T7-1 B17 A35 T5-1 B17 A37 T7-1 B17 A37T5-1 B17 A45 T7-1 B17 A45 T5-1 B17 A46 T7-1 B17 A46 T5-1 B17 A49 T7-1B17 A49 T5-1 B17 A54 T7-1 B17 A54 T5-1 B17 A66 T7-1 B17 A66 T5-1 B17 A67T7-1 B17 A67 T5-1 B17 A68 T7-1 B17 A68 T5-1 B17 A69 T7-1 B17 A69 T5-1B17 A70 T7-1 B17 A70 T5-1 B17 A76 T7-1 B17 A76 T5-1 B17 A77 T7-1 B17 A77T5-1 B17 A78 T7-1 B17 A78 T5-1 B17  A106 T7-1 B17  A106 T5-1 B17  A110T7-1 B17  A110

 

TABLE 21 T1-1 B24 A2 T2-1 B24 A2 T1-1 B24 A5 T2-1 B24 A5 T1-1 B24 A35T2-1 B24 A35 T1-1 B24 A37 T2-1 B24 A37 T1-1 B24 A45 T2-1 B24 A45 T1-1B24 A46 T2-1 B24 A46 T1-1 B24 A49 T2-1 B24 A49 T1-1 B24 A54 T2-1 B24 A54T1-1 B24 A66 T2-1 B24 A66 T1-1 B24 A67 T2-1 B24 A67 T1-1 B24 A68 T2-1B24 A68 T1-1 B24 A69 T2-1 B24 A69 T1-1 B24 A70 T2-1 B24 A70 T1-1 B24 A76T2-1 B24 A76 T1-1 B24 A77 T2-1 B24 A77 T1-1 B24 A78 T2-1 B24 A78 T1-1B24 A106 T2-1 B24 A106 T1-1 B24 A110 T2-1 B24 A110 T2-2 B24 A2 T2-3 B24A2 T2-2 B24 A5 T2-3 B24 A5 T2-2 B24 A35 T2-3 B24 A35 T2-2 B24 A37 T2-3B24 A37 T2-2 B24 A45 T2-3 B24 A45 T2-2 B24 A46 T2-3 B24 A46 T2-2 B24 A49T2-3 B24 A49 T2-2 B24 A54 T2-3 B24 A54 T2-2 B24 A66 T2-3 B24 A66 T2-2B24 A67 T2-3 B24 A67 T2-2 B24 A68 T2-3 B24 A68 T2-2 B24 A69 T2-3 B24 A69T2-2 B24 A70 T2-3 B24 A70 T2-2 B24 A76 T2-3 B24 A76 T2-2 B24 A77 T2-3B24 A77 T2-2 B24 A78 T2-3 B24 A78 T2-2 B24 A106 T2-3 B24 A106 T2-2 B24A110 T2-3 B24 A110 T2-4 B24 A2 T2-5 B24 A2 T2-4 B24 A5 T2-5 B24 A5 T2-4B24 A35 T2-5 B24 A35 T2-4 B24 A37 T2-5 B24 A37 T2-4 B24 A45 T2-5 B24 A45T2-4 B24 A46 T2-5 B24 A46 T2-4 B24 A49 T2-5 B24 A49

 

TABLE 22 T2-4 B24 A54 T2-5 B24 A54 T2-4 B24 A66 T2-5 B24 A66 T2-4 B24A67 T2-5 B24 A67 T2-4 B24 A68 T2-5 B24 A68 T2-4 B24 A69 T2-5 B24 A69T2-4 B24 A70 T2-5 B24 A70 T2-4 B24 A76 T2-5 B24 A76 T2-4 B24 A77 T2-5B24 A77 T2-4 B24 A78 T2-5 B24 A78 T2-4 B24 A106 T2-5 B24 A106 T2-4 B24A110 T2-5 B24 A110 T5-1 B24 A2 T7-1 B24 A2 T5-1 B24 A5 T7-1 B24 A5 T5-1B24 A35 T7-1 B24 A35 T5-1 B24 A37 T7-1 B24 A37 T5-1 B24 A45 T7-1 B24 A45T5-1 B24 A46 T7-1 B24 A46 T5-1 B24 A49 T7-1 B24 A49 T5-1 B24 A54 T7-1B24 A54 T5-1 B24 A66 T7-1 B24 A66 T5-1 B24 A67 T7-1 B24 A67 T5-1 B24 A68T7-1 B24 A68 T5-1 B24 A69 T7-1 B24 A69 T5-1 B24 A70 T7-1 B24 A70 T5-1B24 A76 T7-1 B24 A76 T5-1 B24 A77 T7-1 B24 A77 T5-1 B24 A78 T7-1 B24 A78T5-1 B24 A106 T7-1 B24 A106 T5-1 B24 A110 T7-1 B24 A110 T1-1 B28 A2 T2-1B28 A2 T1-1 B28 A5 T2-1 B28 A5 T1-1 B28 A35 T2-1 B28 A35 T1-1 B28 A37T2-1 B28 A37 T1-1 B28 A45 T2-1 B28 A45 T1-1 B28 A46 T2-1 B28 A46 T1-1B28 A49 T2-1 B28 A49 T1-1 B28 A54 T2-1 B28 A54 T1-1 B28 A66 T2-1 B28 A66T1-1 B28 A67 T2-1 B28 A67 T1-1 B28 A68 T2-1 B28 A68 T1-1 B28 A69 T2-1B28 A69 T1-1 B28 A70 T2-1 B28 A70 T1-1 B28 A76 T2-1 B28 A76

 

TABLE 23 T1-1 B28 A77 T2-1 B28 A77 T1-1 B28 A78 T2-1 B28 A78 T1-1 B28A106 T2-1 B28 A106 T1-1 B28 A110 T2-1 B28 A110 T2-2 B28 A2 T2-3 B28 A2T2-2 B28 A5 T2-3 B28 A5 T2-2 B28 A35 T2-3 B28 A35 T2-2 B28 A37 T2-3 B28A37 T2-2 B28 A45 T2-3 B28 A45 T2-2 B28 A46 T2-3 B28 A46 T2-2 B28 A49T2-3 B28 A49 T2-2 B28 A54 T2-3 B28 A54 T2-2 B28 A66 T2-3 B28 A66 T2-2B28 A67 T2-3 B28 A67 T2-2 B28 A68 T2-3 B28 A68 T2-2 B28 A69 T2-3 B28 A69T2-2 B28 A70 T2-3 B28 A70 T2-2 B28 A76 T2-3 B28 A76 T2-2 B28 A77 T2-3B28 A77 T2-2 B28 A78 T2-3 B28 A78 T2-2 B28 A106 T2-3 B28 A106 T2-2 B28A110 T2-3 B28 A110 T2-4 B28 A2 T2-5 B28 A2 T2-4 B28 A5 T2-5 B28 A5 T2-4B28 A35 T2-5 B28 A35 T2-4 B28 A37 T2-5 B28 A37 T2-4 B28 A45 T2-5 B28 A45T2-4 B28 A46 T2-5 B28 A46 T2-4 B28 A49 T2-5 B28 A49 T2-4 B28 A54 T2-5B28 A54 T2-4 B28 A66 T2-5 B28 A66 T2-4 B28 A67 T2-5 B28 A67 T2-4 B28 A68T2-5 B28 A68 T2-4 B28 A69 T2-5 B28 A69 T2-4 B28 A70 T2-5 B28 A70 T2-4B28 A76 T2-5 B28 A76 T2-4 B28 A77 T2-5 B28 A77 T2-4 B28 A78 T2-5 B28 A78T2-4 B28 A106 T2-5 B28 A106 T2-4 B28 A110 T2-5 B28 A110 T5-1 B28 A2 T7-1B28 A2 T5-1 B28 A5 T7-1 B28 A5 T5-1 B28 A35 T7-1 B28 A35

 

TABLE 24 T5-1 B28 A37 T7-1 B28 A37 T5-1 B28 A45 T7-1 B28 A45 T5-1 B28A46 T7-1 B28 A46 T5-1 B28 A49 T7-1 B28 A49 T5-1 B28 A54 T7-1 B28 A54T5-1 B28 A66 T7-1 B28 A66 T5-1 B28 A67 T7-1 B28 A67 T5-1 B28 A68 T7-1B28 A68 T5-1 B28 A69 T7-1 B28 A69 T5-1 B28 A70 T7-1 B28 A70 T5-1 B28 A76T7-1 B28 A76 T5-1 B28 A77 T7-1 B28 A77 T5-1 B28 A78 T7-1 B28 A78 T5-1B28 A106 T7-1 B28 A106 T5-1 B28 A110 T7-1 B28 A110 T1-1 B29 A2 T2-1 B29A2 T1-1 B29 A5 T2-1 B29 A5 T1-1 B29 A35 T2-1 B29 A35 T1-1 B29 A37 T2-1B29 A37 T1-1 B29 A45 T2-1 B29 A45 T1-1 B29 A46 T2-1 B29 A46 T1-1 B29 A49T2-1 B29 A49 T1-1 B29 A54 T2-1 B29 A54 T1-1 B29 A66 T2-1 B29 A66 T1-1B29 A67 T2-1 B29 A67 T1-1 B29 A68 T2-1 B29 A68 T1-1 B29 A69 T2-1 B29 A69T1-1 B29 A70 T2-1 B29 A70 T1-1 B29 A76 T2-1 B29 A76 T1-1 B29 A77 T2-1B29 A77 T1-1 B29 A78 T2-1 B29 A78 T1-1 B29 A106 T2-1 B29 A106 T1-1 B29A110 T2-1 B29 A110 T2-2 B29 A2 T2-3 B29 A2 T2-2 B29 A5 T2-3 B29 A5 T2-2B29 A35 T2-3 B29 A35 T2-2 B29 A37 T2-3 B29 A37 T2-2 B29 A45 T2-3 B29 A45T2-2 B29 A46 T2-3 B29 A46 T2-2 B29 A49 T2-3 B29 A49 T2-2 B29 A54 T2-3B29 A54 T2-2 B29 A66 T2-3 B29 A66 T2-2 B29 A67 T2-3 B29 A67

 

TABLE 25 T2-2 B29 A68 T2-3 B29 A68 T2-2 B29 A69 T2-3 B29 A69 T2-2 B29A70 T2-3 B29 A70 T2-2 B29 A76 T2-3 B29 A76 T2-2 B29 A77 T2-3 B29 A77T2-2 B29 A78 T2-3 B29 A78 T2-2 B29 A106 T2-3 B29 A106 T2-2 B29 A110 T2-3B29 A110 T2-4 B29 A2 T2-5 B29 A2 T2-4 B29 A5 T2-5 B29 A5 T2-4 B29 A35T2-5 B29 A35 T2-4 B29 A37 T2-5 B29 A37 T2-4 B29 A45 T2-5 B29 A45 T2-4B29 A46 T2-5 B29 A46 T2-4 B29 A49 T2-5 B29 A49 T2-4 B29 A54 T2-5 B29 A54T2-4 B29 A66 T2-5 B29 A66 T2-4 B29 A67 T2-5 B29 A67 T2-4 B29 A68 T2-5B29 A68 T2-4 B29 A69 T2-5 B29 A69 T2-4 B29 A76 T2-5 B29 A70 T2-4 B29 A76T2-5 B29 A76 T2-4 B29 A77 T2-5 B29 A77 T2-4 B29 A78 T2-5 B29 A78 T2-4B29 A106 T2-5 B29 A106 T2-4 B29 A110 T2-5 B29 A110 T5-1 B29 A2 T7-1 B29A2 T5-1 B29 A5 T7-1 B29 A5 T5-1 B29 A35 T7-1 B29 A35 T5-1 B29 A37 T7-1B29 A37 T5-1 B29 A45 T7-1 B29 A45 T5-1 B29 A46 T7-1 B29 A46 T5-1 B29 A49T7-1 B29 A49 T5-1 B29 A54 T7-1 B29 A54 T5-1 B29 A66 T7-1 B29 A66 T5-1B29 A67 T7-1 B29 A67 T5-1 B29 A68 T7-1 B29 A68 T5-1 B29 A69 T7-1 B29 A69T5-1 B29 A70 T7-1 B29 A70 T5-1 B29 A76 T7-1 B29 A76 T5-1 B29 A77 T7-1B29 A77 T5-1 B29 A78 T7-1 B29 A78 T5-1 B29 A106 T7-1 B29 A106

 

TABLE 26 T5-1 B29 A110 T7-1 B29 A110 T1-1 B30 A2 T2-1 B30 A2 T1-1 B30 A5T2-1 B30 A5 T1-1 B30 A35 T2-1 B30 A35 T1-1 B30 A37 T2-1 B30 A37 T1-1 B30A45 T2-1 B30 A45 T1-1 B30 A46 T2-1 B30 A46 T1-1 B30 A49 T2-1 B30 A49T1-1 B30 A54 T2-1 B30 A54 T1-1 B30 A66 T2-1 B30 A66 T1-1 B30 A67 T2-1B30 A67 T1-1 B30 A68 T2-1 B30 A68 T1-1 B30 A69 T2-1 B30 A69 T1-1 B30 A70T2-1 B30 A70 T1-1 B30 A76 T2-1 B30 A76 T1-1 B30 A77 T2-1 B30 A77 T1-1B30 A78 T2-1 B30 A78 T1-1 B30 A106 T2-1 B30 A106 T1-1 B30 A110 T2-1 B30A110 T2-2 B30 A2 T2-3 B30 A2 T2-2 B30 A5 T2-3 B30 A5 T2-2 B30 A35 T2-3B30 A35 T2-2 B30 A37 T2-3 B30 A37 T2-2 B30 A45 T2-3 B30 A45 T2-2 B30 A46T2-3 B30 A46 T2-2 B30 A49 T2-3 B30 A49 T2-2 B30 A54 T2-3 B30 A54 T2-2B30 A66 T2-3 B30 A66 T2-2 B30 A67 T2-3 B30 A67 T2-2 B30 A68 T2-3 B30 A68T2-2 B30 A69 T2-3 B30 A69 T2-2 B30 A70 T2-3 B30 A70 T2-2 B30 A76 T2-3B30 A76 T2-2 B30 A77 T2-3 B30 A77 T2-2 B30 A78 T2-3 B30 A78 T2-2 B30A106 T2-3 B30 A106 T2-2 B30 A110 T2-3 B30 A110 T2-4 B30 A2 T2-5 B30 A2T2-4 B30 A5 T2-5 B30 A5 T2-4 B30 A35 T2-5 B30 A35 T2-4 B30 A37 T2-5 B30A37 T2-4 B30 A45 T2-5 B30 A45 T2-4 B30 A46 T2-5 B30 A46

 

TABLE 27 T2-4 B30 A49 T2-5 B30 A49 T2-4 B30 A54 T2-5 B30 A54 T2-4 B30A66 T2-5 B30 A66 T2-4 B30 A67 T2-5 B30 A67 T2-4 B30 A68 T2-5 B30 A68T2-4 B30 A69 T2-5 B30 A69 T2-4 B30 A70 T2-5 B30 A70 T2-4 B30 A76 T2-5B30 A76 T2-4 B30 A77 T2-5 B30 A77 T2-4 B30 A78 T2-5 B30 A78 T2-4 B30A106 T2-5 B30 A106 T2-4 B30 A110 T2-5 B30 A110 T5-1 B30 A2 T7-1 B30 A2T5-1 B30 A5 T7-1 B30 A5 T5-1 B30 A35 T7-1 B30 A35 T5-1 B30 A37 T7-1 B30A37 T5-1 B30 A45 T7-1 B30 A45 T5-1 B30 A46 T7-1 B30 A46 T5-1 B36 A49T7-1 B30 A49 T5-1 B30 A54 T7-1 B30 A54 T5-1 B30 A66 T7-1 B30 A66 T5-1B30 A67 T7-1 B30 A67 T5-1 B36 A68 T7-1 B30 A68 T5-1 B30 A69 T7-1 B30 A69T5-1 B30 A70 T7-1 B30 A70 T5-1 B30 A76 T7-1 B30 A76 T5-1 B30 A77 T7-1B30 A77 T5-1 B30 A78 T7-1 B30 A78 T5-1 B30 A106 T7-1 B30 A106 T5-1 B30A110 T7-1 B30 A110 T1-1 B31 A2 T2-1 B31 A2 T1-1 B31 A5 T2-1 B31 A5 T1-1B31 A35 T2-1 B31 A35 T1-1 B31 A37 T2-1 B31 A37 T1-1 B31 A45 T2-1 B31 A45T1-1 B31 A46 T2-1 B31 A46 T1-1 B31 A49 T2-1 B31 A49 T1-1 B31 A54 T2-1B31 A54 T1-1 B31 A66 T2-1 B31 A66 T1-1 B31 A67 T2-1 B31 A67 T1-1 B31 A68T2-1 B31 A68 T1-1 B31 A69 T2-1 B31 A69 T1-1 B31 A70 T2-1 B31 A70

 

TABLE 28 T1-1 B31 A76 T2-1 B31 A76 T1-1 B31 A77 T2-1 B31 A77 T1-1 B31A78 T2-1 B31 A78 T1-1 B31 A106 T2-1 B31 A106 T1-1 B31 A110 T2-1 B31 A110T2-2 B31 A2 T2-3 B31 A2 T2-2 B31 A5 T2-3 B31 A5 T2-2 B31 A35 T2-3 B31A35 T2-2 B31 A37 T2-3 B31 A37 T2-2 B31 A45 T2-3 B31 A45 T2-2 B31 A46T2-3 B31 A46 T2-2 B31 A49 T2-3 B31 A49 T2-2 B31 A54 T2-3 B31 A54 T2-2B31 A66 T2-3 B31 A66 T2-2 B31 A67 T2-3 B31 A67 T2-2 B31 A68 T2-3 B31 A68T2-2 B31 A69 T2-3 B31 A69 T2-2 B31 A70 T2-3 B31 A70 T2-2 B31 A76 T2-3B31 A76 T2-2 B31 A77 T2-3 B31 A77 T2-2 B31 A78 T2-3 B31 A78 T2-2 B31A106 T2-3 B31 A106 T2-2 B31 A110 T2-3 B31 A110 T2-4 B31 A2 T2-5 B31 A2T2-4 B31 A5 T2-5 B31 A5 T2-4 B31 A35 T2-5 B31 A35 T2-4 B31 A37 T2-5 B31A37 T2-4 B31 A45 T2-5 B31 A45 T2-4 B31 A46 T2-5 B31 A46 T2-4 B31 A49T2-5 B31 A49 T2-4 B31 A54 T2-5 B31 A54 T2-4 B31 A66 T2-5 B31 A66 T2-4B31 A67 T2-5 B31 A67 T2-4 B31 A68 T2-5 B31 A68 T2-4 B31 A69 T2-5 B31 A69T2-4 B31 A70 T2-5 B31 A70 T2-4 B31 A76 T2-5 B31 A76 T2-4 B31 A77 T2-5B31 A77 T2-4 B31 A78 T2-5 B31 A78 T2-4 B31 A106 T2-5 B31 A106 T2-4 B31A110 T2-5 B31 A110 T5-1 B31 A2 T7-1 B31 A2 T5-1 B31 A5 T7-1 B31 A5

 

TABLE 29 T5-1 B31 A35 T7-1 B31 A35 T5-1 B31 A37 T7-1 B31 A37 T5-1 B31A45 T7-1 B31 A45 T5-1 B31 A46 T7-1 B31 A46 T5-1 B31 A49 T7-1 B31 A49T5-1 B31 A54 T7-1 B31 A54 T5-1 B31 A66 T7-1 B31 A66 T5-1 B31 A67 T7-1B31 A67 T5-1 B31 A68 T7-1 B31 A68 T5-1 B31 A69 T7-1 B31 A69 T5-1 B31 A70T7-1 B31 A70 T5-1 B31 A76 T7-1 B31 A76 T5-1 B31 A77 T7-1 B31 A77 T5-1B31 A78 T7-1 B31 A78 T5-1 B31 A106 T7-1 B31 A106 T5-1 B31 A110 T7-1 B31A110 T1-1 B32 A2 T2-1 B32 A2 T1-1 B32 A5 T2-1 B32 A5 T1-1 B32 A35 T2-1B32 A35 T1-1 B32 A37 T2-1 B32 A37 T1-1 B32 A45 T2-1 B32 A45 T1-1 B32 A46T2-1 B32 A46 T1-1 B32 A49 T1-1 B32 A49 T1-1 B32 A54 T2-1 B32 A54 T1-1B32 A66 T2-1 B32 A66 T1-1 B32 A67 T2-1 B32 A67 T1-1 B32 A68 T2-1 B32 A68T1-1 B32 A69 T2-1 B32 A69 T1-1 B32 A70 T2-1 B32 A76 T1-1 B32 A76 T2-1B32 A76 T1-1 B32 A77 T2-1 B32 A77 T1-1 B32 A78 T2-1 B32 A78 T1-1 B32A106 T2-1 B32 A106 T1-1 B32 A110 T2-1 B32 A110 T2-2 B32 A2 T2-3 B32 A2T2-2 B32 A5 T2-3 B32 A5 T2-2 B32 A5 T2-3 B32 A35 T2-2 B32 A37 T2-3 B32A37 T2-2 B32 A45 T2-3 B32 A45 T2-2 B32 A46 T2-3 B32 A46 T2-2 B32 A49T2-3 B32 A49 T2-2 B32 A54 T2-3 B32 A54 T2-2 B32 A66 T2-3 B32 A66

 

TABLE 30 T2-2 B32 A67 T2-3 B32 A67 T2-2 B32 A68 T2-3 B32 A68 T2-2 B32A69 T2-3 B32 A69 T2-2 B32 A70 T2-3 B32 A70 T2-2 B32 A76 T2-3 B32 A76T2-2 B32 A77 T2-3 B32 A77 T2-2 B32 A78 T2-3 B32 A78 T2-2 B32 A106 T2-3B32 A106 T2-2 B32 A110 T2-3 B32 A110 T2-4 B32 A2 T2-5 B32 A2 T2-4 B32 A5T2-5 B32 A5 T2-4 B32 A35 T2-5 B32 A35 T2-4 B32 A37 T2-5 B32 A37 T2-4 B32A45 T2-5 B32 A45 T2-4 B32 A46 T2-5 B32 A46 T2-4 B32 A49 T2-5 B32 A49T2-4 B32 A54 T2-5 B32 A54 T2-4 B32 A66 T2-5 B32 A66 T2-4 B32 A67 T2-5B32 A67 T2-4 B32 A68 T2-5 B32 A68 T2-4 B32 A69 T2-5 B32 A69 T2-4 B32 A70T2-5 B32 A70 T2-4 B32 A76 T2-5 B32 A76 T2-4 B32 A77 T2-5 B32 A77 T2-4B32 A78 T2-5 B32 A78 T2-4 B32 A106 T2-5 B32 A106 T2-4 B32 A110 T2-5 B32A110 T5-1 B32 A2 T7-1 B32 A2 T5-1 B32 A5 T7-1 B32 A5 T5-1 B32 A35 T7-1B32 A35 T5-1 B32 A37 T7-1 B32 A37 T5-1 B32 A45 T7-1 B32 A45 T5-1 B32 A46T7-1 B32 A46 T5-1 B32 A49 T7-1 B32 A49 T5-1 B32 A54 T7-1 B32 A54 T5-1B32 A66 T7-1 B32 A66 T5-1 B32 A67 T7-1 B32 A67 T5-1 B32 A68 T7-1 B32 A68T5-1 B32 A69 T7-1 B32 A69 T5-1 B32 A70 T7-1 B32 A70 T5-1 B32 A76 T7-1B32 A76 T5-1 B32 A77 T7-1 B32 A77 T5-1 B32 A78 T7-1 B32 A78

 

TABLE 31 T5-1 B32 A106 T7-1 B32 A106 T5-1 B32 A110 T7-1 B32 A110 T1-1B33 A2 T2-1 B33 A2 T1-1 B33 A5 T2-1 B33 A5 T1-1 B33 A35 T2-1 B33 A35T1-1 B33 A37 T2-1 B33 A37 T1-1 B33 A45 T2-1 B33 A45 T1-1 B33 A46 T2-1B33 A46 T1-1 B33 A49 T2-1 B33 A49 T1-1 B33 A54 T2-1 B33 A54 T1-1 B33 A66T2-1 B33 A66 T1-1 B33 A67 T2-1 B33 A67 T1-1 B33 A68 T2-1 B33 A68 T1-1B33 A69 T2-1 B33 A69 T1-1 B33 A70 T2-1 B33 A70 T1-1 B33 A76 T2-1 B33 A76T1-1 B33 A77 T2-1 B33 A77 T1-1 B33 A78 T2-1 B33 A78 T1-1 B33 A106 T2-1B33 A106 T1-1 B33 A110 T2-1 B33 A110 T2-2 B33 A2 T2-3 B33 A2 T2-2 B33 A5T2-3 B33 A5 T2-2 B33 A35 T2-3 B33 A35 T2-2 B33 A37 T2-3 B33 A37 T2-2 B33A45 T2-3 B33 A45 T2-2 B33 A46 T2-3 B33 A46 T2-2 B33 A49 T2-3 B33 A49T2-2 B33 A54 T2-3 B33 A54 T2-2 B33 A66 T2-3 B33 A66 T2-2 B33 A67 T2-3B33 A67 T2-2 B33 A68 T2-3 B33 A68 T2-2 B33 A69 T2-3 B33 A69 T2-2 B33 A70T2-3 B33 A70 T2-2 B33 A76 T2-3 B33 A76 T2-2 B33 A77 T2-3 B33 A77 T2-2B33 A78 T2-3 B33 A78 T2-2 B33 A106 T2-3 B33 A106 T2-2 B33 A110 T2-3 B33A110 T2-4 B33 A2 T2-5 B33 A2 T2-4 B33 A5 T2-5 B33 A5 T2-4 B33 A35 T2-5B33 A35 T2-4 B33 A37 T2-5 B33 A37 T2-4 B33 A45 T2-5 B33 A45

 

TABLE 32 T2-4 B33 A46 T2-5 B33 A46 T2-4 B33 A49 T2-5 B33 A49 T2-4 B33A54 T2-5 B33 A54 T2-4 B33 A66 T2-5 B33 A66 T2-4 B33 A67 T2-5 B33 A67T2-4 B33 A68 T2-5 B33 A68 T2-4 B33 A69 T2-5 B33 A69 T2-4 B33 A70 T2-5B33 A70 T2-4 B33 A76 T2-5 B33 A76 T2-4 B33 A77 T2-5 B33 A77 T2-4 B33 A78T2-5 B33 A78 T2-4 B33 A106 T2-5 B33 A106 T2-4 B33 A110 T2-5 B33 A110T5-1 B33 A2 T7-1 B33 A2 T5-1 B33 A5 T7-1 B33 A5 T5-1 B33 A35 T7-1 B33A35 T5-1 B33 A37 T7-1 B33 A37 T5-1 B33 A45 T7-1 B33 A45 T5-1 B33 A46T7-1 B33 A46 T5-1 B33 A49 T7-1 B33 A49 T5-1 B33 A54 T7-1 B33 A54 T5-1B33 A66 T7-1 B33 A66 T5-1 B33 A67 T7-1 B33 A67 T5-1 B33 A68 T7-1 B33 A68T5-1 B33 A69 T7-1 B33 A69 T5-1 B33 A70 T7-1 B33 A70 T5-1 B33 A76 T7-1B33 A76 T5-1 B33 A77 T7-1 B33 A77 T5-1 B33 A78 T7-1 B33 A78 T5-1 B33A106 T7-1 B33 A106 T5-1 B33 A110 T7-1 B33 A110 T1-1 B34 A2 T2-1 B34 A2T1-1 B34 A5 T2-1 B34 A5 T1-1 B34 A35 T2-1 B34 A35 T1-1 B34 A37 T2-1 B34A37 T1-1 B34 A45 T2-1 B34 A45 T1-1 B34 A46 T2-1 B34 A46 T1-1 B34 A49T2-1 B34 A49 T1-1 B34 A54 T2-1 B34 A54 T1-1 B34 A66 T2-1 B34 A66 T1-1B34 A67 T2-1 B34 A67 T1-1 B34 A68 T2-1 B34 A68 T1-1 B34 A69 T2-1 B34 A69

 

TABLE 33 T1-1 B34 A70 T2-1 B34 A70 T1-1 B34 A76 T2-1 B34 A76 T1-1 B34A77 T2-1 B34 A77 T1-1 B34 A78 T2-1 B34 A78 T1-1 B34 A106 T2-1 B34 A106T1-1 B34 A110 T2-1 B34 A110 T2-2 B34 A2 T2-3 B34 A2 T2-2 B34 A5 T2-3 B34A5 T2-2 B34 A35 T2-3 B34 A35 T2-2 B34 A37 T2-3 B34 A37 T2-2 B34 A45 T2-3B34 A45 T2-2 B34 A46 T2-3 B34 A46 T2-2 B34 A49 T2-3 B34 A49 T2-2 B34 A54T2-3 B34 A54 T2-2 B34 A66 T2-3 B34 A66 T2-2 B34 A67 T2-3 B34 A67 T2-2B34 A68 T2-3 B34 A68 T2-2 B34 A69 T2-3 B34 A69 T2-2 B34 A70 T2-3 B34 A70T2-2 B34 A76 T2-3 B34 A76 T2-2 B34 A77 T2-3 B34 A77 T2-2 B34 A78 T2-3B34 A78 T2-2 B34 A106 T2-3 B34 A106 T2-2 B34 A110 T2-3 B34 A110 T2-4 B34A2 T2-5 B34 A2 T2-4 B34 A5 T2-5 B34 A5 T2-4 B34 A35 T2-5 B34 A35 T2-4B34 A37 T2-5 B34 A37 T2-4 B34 A45 T2-5 B34 A45 T2-4 B34 A46 T2-5 B34 A46T2-4 B34 A49 T2-5 B34 A49 T2-4 B34 A54 T2-5 B34 A54 T2-4 B34 A66 T2-5B34 A66 T2-4 B34 A67 T2-5 B34 A67 T2-4 B34 A68 T2-5 B34 A68 T2-4 B34 A69T2-5 B34 A69 T2-4 B34 A70 T2-5 B34 A70 T2-4 B34 A76 T2-5 B34 A76 T2-4B34 A77 T2-5 B34 A77 T2-4 B34 A78 T2-5 B34 A78 T2-4 B34 A106 T2-5 B34A106 T2-4 B34 A110 T2-5 B34 A110

 

TABLE 34 T5-1 B34 A2 T7-1 B34 A2 T5-1 B34 A5 T7-1 B34 A5 T5-1 B34 A35T7-1 B34 A35 T5-1 B34 A37 T7-1 B34 A37 T5-1 B34 A45 T7-1 B34 A45 T5-1B34 A46 T7-1 B34 A46 T5-1 B34 A49 T7-1 B34 A49 T5-1 B34 A54 T7-1 B34 A54T5-1 B34 A66 T7-1 B34 A66 T5-1 B34 A67 T7-1 B34 A67 T5-1 B34 A68 77-1B34 A68 T5-1 B34 A69 T7-1 B34 A69 T5-1 B34 A70 T7-1 B34 A70 T5-1 B34 A76T7-1 B34 A76 T5-1 B34 A77 T7-1 B34 A77 T5-1 B34 A78 T7-1 B34 A78 T5-1B34 A106 T7-1 B34 A106 T5-1 B34 A110 T7-1 B34 A110 T1-1 B35 A2 T2-1 B35A2 T1-1 B35 A5 T2-1 B35 A5 T1-1 B35 A35 T2-1 E35 A35 T1-1 B35 A37 T2-1B35 A37 T1-1 B35 A45 T2-1 B35 A45 T1-1 B35 A46 T2-1 B35 A46 T1-1 B35 A49T2-1 B35 A49 T1-1 B35 A54 T2-1 B35 A54 T1-1 B35 A66 T2-1 B35 A66 T1-1B35 A67 T2-1 B35 A67 T1-1 B35 A68 T2-1 B35 A68 T1-1 P35 A69 T2-1 B35 A69T1-1 B35 A70 T2-1 B35 A70 T1-1 B35 A76 T2-1 B35 A76 T1-1 B35 A77 T2-1B35 A77 T1-1 B35 A78 T2-1 B35 A78 T1-1 B35 A106 T2-1 B35 A106 T1-1 B35A110 T2-1 B35 A110 T2-2 B35 A2 T2-3 B35 A2 T2-2 B35 A5 T2-3 B35 A5 T2-2B35 A35 T2-3 B35 A35 T2-2 B35 A37 T2-3 B35 A37 T2-2 B35 A45 T2-3 B35 A45T2-2 B35 A46 T2-3 B35 A46 T2-2 B35 A49 T2-3 B35 A49

 

TABLE 35 T2-2 B35 A54 T2-3 B35 A54 T2-2 B35 A66 T2-3 B35 A66 T2-2 B35A67 T2-3 B35 A67 T2-2 B35 A68 T2-3 B35 A68 T2-2 B35 A69 T2-3 B35 A69T2-2 B35 A70 T2-3 B35 A70 T2-2 B35 A76 T2-3 B35 A76 T2-2 B35 A77 T2-3B35 A77 T2-2 B35 A78 T2-3 B35 A78 T2-2 B35 A106 T2-3 B35 A106 T2-2 B35A110 T2-3 B35 A110 T2-4 B35 A2 T2-5 B35 A2 T2-4 B35 A5 T2-5 B35 A5 T2-4B35 A35 T2-5 B35 A35 T2-4 B35 A37 T2-5 B35 A37 T2-4 B35 A45 T2-5 B35 A45T2-4 B35 A46 T2-5 B35 A46 T2-4 B35 A49 T2-5 B35 A49 T2-4 B35 A54 T2-5B35 A54 T2-4 B35 A66 T2-5 B35 A66 T2-4 B35 A67 T2-5 B35 A67 T2-4 B35 A68T2-5 B35 A68 T2-4 B35 A69 T2-5 B35 A69 T2-4 B35 A70 T2-5 B35 A70 T2-4B35 A76 T2-5 B35 A76 T2-4 B35 A77 T2-5 B35 A77 T2-4 B35 A78 T2-5 B35 A78T2-4 B35 A106 T2-5 B35 A106 T2-4 B35 A110 T2-5 B35 A110 T5-1 B35 A2 T7-1B35 A2 T5-1 B35 A5 T7-1 B35 A5 T5-1 B35 A35 T7-1 B35 A35 T5-1 B35 A37T7-1 B35 A37 T5-1 B35 A45 T7-1 B35 A45 T5-1 B35 A46 T7-1 B35 A46 T5-1B35 A49 T7-1 B35 A49 T5-1 B35 A54 T7-1 B35 A54 T5-1 B35 A66 T7-1 B35 A66T5-1 B35 A67 T7-1 B35 A67 T5-1 B35 A68 T7-1 B35 A68 T5-1 B35 A69 T7-1B35 A69 T5-1 B35 A70 T7-1 B35 A70 T5-1 B35 A76 T7-1 B35 A76

 

TABLE 36 T5-1 B35 A77 T7-1 B35 A77 T5-1 B35 A78 T7-1 B35 A78 T5-1 B35A106 T7-1 B35 A106 T5-1 B35 A110 T7-1 B35 A110 T1-1 B36 A2 T2-1 B36 A2T1-1 B36 A5 T2-1 B36 A5 T1-1 B36 A35 T2-1 B36 A35 T1-1 B36 A37 T2-1 B36A37 T1-1 B36 A45 T2-1 B36 A45 T1-1 B36 A46 T2-1 B36 A46 T1-1 B36 A49T2-1 B36 A49 T1-1 B36 A54 T2-1 B36 A54 T1-1 B36 A66 T2-1 B36 A66 T1-1B36 A67 T2-1 B36 A67 T1-1 B36 A68 T2-1 B36 A68 T1-1 B36 A69 T2-1 B36 A69T1-1 B36 A70 T2-1 B36 A70 T1-1 B36 A76 T2-1 B36 A76 T1-1 B36 A77 T2-1B36 A77 T1-1 B36 A78 T2-1 B36 A78 T1-1 B36 A106 T2-1 B36 A106 T1-1 B36A110 T2-1 B36 A110 T2-2 B36 A2 T2-3 B36 A2 T2-2 B36 A5 T2-3 B36 A5 T2-2B36 A35 T2-3 B36 A35 T2-2 B36 A37 T2-3 B36 A37 T2-2 B36 A45 T2-3 B36 A45T2-2 B36 A46 T2-3 B36 A46 T2-2 B36 A49 T2-3 B36 A49 T2-2 B36 A54 T2-3B36 A54 T2-2 B36 A66 T2-3 B36 A66 T2-2 B36 A67 T2-3 B36 A67 T2-2 B36 A68T2-3 B36 A68 T2-2 B36 A69 T2-3 B36 A69 T2-2 B36 A70 T2-3 B36 A70 T2-2B36 A76 T2-3 B36 A76 T2-2 B36 A77 T2-3 B36 A77 T2-2 B36 A78 T2-3 B36 A78T2-2 B36 A106 T2-3 B36 A106 T2-2 B36 A110 T2-3 B36 A110 T2-4 B36 A2 T2-5B36 A2 T2-4 B36 A5 T2-5 B36 A5 T2-4 B36 A35 T2-5 B36 A35

 

TABLE 37 T2-4 B36 A37 T2-5 B36 A37 T2-4 B36 A45 T2-5 B36 A45 T2-4 B36A46 T2-5 B36 A46 T2-4 B36 A49 T2-5 B36 A49 T2-4 B36 A54 T2-5 B36 A54T2-4 B36 A66 T2-5 B36 A66 T2-4 B36 A67 T2-5 B36 A67 T2-4 B36 A65 T2-5B36 A68 T2-4 B36 A69 T2-5 B36 A69 T2-4 B36 A70 T2-5 B36 A70 T2-4 B36 A76T2-5 B36 A76 T2-4 B36 A77 T2-5 B36 A77 T2-4 B36 A78 T2-5 B36 A78 T2-4B36 A106 T2-5 B36 A106 T2-4 B36 A110 T2-5 B36 A110 T5-1 B36 A2 T7-1 B36A2 T5-1 B36 A5 T7-1 B36 A5 T5-1 B36 A35 T7-1 B36 A35 T5-1 B36 A37 T7-1B36 A37 T5-1 B36 A45 T7-1 B36 A45 T5-1 B36 A46 T7-1 B36 A46 T5-1 B36 A49T7-1 B36 A49 T5-1 B36 A54 T7-1 B36 A54 T5-1 B36 A66 T7-1 B36 A66 T5-1B36 A67 T7-1 B36 A67 T5-1 B36 A68 T7-1 B36 A68 T5-1 B36 A69 T7-1 B36 A69T5-1 B36 A70 T7-1 B36 A70 T5-1 B36 A76 T7-1 B36 A76 T5-1 B36 A77 T7-1B36 A77 T5-1 B36 A78 T7-1 B36 A78 T5-1 B36 A106 T7-1 B36 A106 T5-1 B36A110 T7-1 B36 A110 T1-1 B37 A2 T2-1 B37 A2 T1-1 B37 A5 T2-1 B37 A5 T1-1B37 A35 T2-1 B37 A35 T1-1 B37 A37 T2-1 B37 A37 T1-1 B37 A45 T2-1 B37 A45T1-1 B37 A46 T2-1 B37 A46 T1-1 B37 A49 T2-1 B37 A49 T1-1 B37 A54 T2-1B37 A54 T1-1 B37 A66 T2-1 B37 A66 T1-1 B37 A67 T2-1 B37 A67

 

TABLE 38 T1-1 B37 A68 T2-1 B37 A68 T1-1 B37 A69 T2-1 B37 A69 T1-1 B37A70 T2-1 B37 A70 T1-1 B37 A76 T2-1 B37 A76 T1-1 B37 A77 T2-1 B37 A77T1-1 B37 A78 T2-1 B37 A78 T1-1 B37 A106 T2-1 B37 A106 T1-1 B37 A110 T2-1B37 A110 T2-2 B37 A2 T2-3 B37 A2 T2-2 B37 A5 T2-3 B37 A5 T2-2 B37 A35T2-3 B37 A35 T2-2 B37 A37 T2-3 B37 A37 T2-2 B37 A45 T2-3 B37 A45 T2-2B37 A46 T2-3 B37 A46 T2-2 B37 A49 T2-3 B37 A49 T2-2 B37 A54 T2-3 B37 A54T2-2 B37 A66 T2-3 B37 A66 T2-2 B37 A67 T2-3 B37 A67 T2-2 B37 A68 T2-3B37 A68 T2-2 B37 A69 T2-3 B37 A69 T2-2 B37 A70 T2-3 B37 A70 T2-2 B37 A76T2-3 B37 A76 T2-2 B37 A77 T2-3 B37 A77 T2-2 B37 A78 T2-3 B37 A78 T2-2B37 A106 T2-3 B37 A106 T2-2 B37 A110 T2-3 B37 A110 T2-4 B37 A2 T2-5 B37A2 T2-4 B37 A5 T2-5 B37 A5 T2-4 B37 A35 T2-5 B37 A35 T2-4 B37 A37 T2-5B37 A37 T2-4 B37 A45 T2-5 B37 A45 T2-4 B37 A46 T2-5 B37 A46 T2-4 B37 A49T2-5 B37 A49 T2-4 B37 A54 T2-5 B37 A54 T2-4 B37 A66 T2-5 B37 A66 T2-4B37 A67 T2-5 B37 A67 T2-4 B37 A68 T2-5 B37 A68 T2-4 B37 A69 T2-5 B37 A69T2-4 B37 A70 T2-5 B37 A70 T2-4 B37 A76 T2-5 B37 A76 T2-4 B37 A77 T2-5B37 A77 T2-4 B37 A78 T2-5 B37 A78 T2-4 B37 A106 T2-5 B37 A106

 

TABLE 39 T2-4 B37 A110 T2-5 B37 A110 T5-1 B37 A2 T7-1 B37 A2 T5-1 B37 A5T7-1 B37 A5 T5-1 B37 A35 T7-1 B37 A35 T5-1 B37 A37 T7-1 B37 A37 T5-1 B37A45 T7-1 B37 A45 T5-1 B37 A46 T7-1 B37 A46 T5-1 B37 A49 T7-1 B37 A49T5-1 B37 A54 T7-1 B37 A54 T5-1 B37 A66 T7-1 B37 A66 T5-1 B37 A67 T7-1B37 A67 T5-1 B37 A68 T7-1 B37 A68 T5-1 B37 A69 T7-1 B37 A69 T5-1 B37 A70T7-1 B37 A70 T5-1 B37 A76 T7-1 B37 A76 T5-1 B37 A77 T7-1 B37 A77 T5-1B37 A78 T7-1 B37 A78 T5-1 B37 A106 T7-1 B37 A106 T5-1 B37 A110 T7-1 B37A110 T1-1 B38 A2 T2-1 B38 A2 T1-1 B38 A5 T2-1 B38 A5 T1-1 B38 A35 T2-1B38 A35 T1-1 B38 A37 T2-1 B38 A37 T1-1 B38 A45 T2-1 B38 A45 T1-1 B38 A46T2-1 B38 A46 T1-1 B38 A49 T2-1 B38 A49 T1-1 B38 A54 T2-1 B38 A54 T1-1B38 A66 T2-1 B38 A66 T1-1 B38 A67 T2-1 B38 A67 T1-1 B38 A68 T2-1 B38 A68T1-1 B38 A69 T2-1 B38 A69 T1-1 B38 A70 T2-1 B38 A70 T1-1 B38 A76 T2-1B38 A76 T1-1 B38 A77 T2-1 B38 A77 T1-1 B38 A78 T2-1 B38 A78 T1-1 B38A106 T2-1 B38 A106 T1-1 B38 A110 T2-1 B38 A110 T2-2 B38 A2 T2-3 B38 A2T2-2 B38 A5 T2-3 B38 A5 T2-2 B38 A35 T2-3 B38 A35 T2-2 B38 A37 T2-3 B38A37 T2-2 B38 A45 T2-3 B38 A45 T2-2 B38 A46 T2-3 B38 A46

 

TABLE 40 T2-2 B38 A49 T2-3 B38 A49 T2-2 B38 A54 T2-3 B38 A54 T2-2 B38A66 T2-3 B38 A66 T2-2 B38 A67 T2-3 B38 A67 T2-2 B38 A68 T2-3 B38 A68T2-2 B38 A69 T2-3 B38 A69 T2-2 B38 A70 T2-3 B38 A70 T2-2 B38 A76 T2-3B38 A76 T2-2 B38 A77 T2-3 B38 A77 T2-2 B38 A78 T2-3 B38 A78 T2-2 B38A106 T2-3 B38 A106 T2-2 B38 A110 T2-3 B38 A110 T2-4 B38 A2 T2-5 B38 A2T2-4 B38 A5 T2-5 B38 A5 T2-4 B38 A35 T2-5 B38 A35 T2-4 B38 A37 T2-5 B38A37 T2-4 B38 A45 T2-5 B38 A45 T2-4 B38 A46 T2-5 B38 A46 T2-4 B38 A49T2-5 B38 A49 T2-4 B38 A54 T2-5 B38 A54 T2-4 B38 A66 T2-5 B38 A66 T2-4B38 A67 T2-5 B38 A67 T2-4 B38 A68 T2-5 B38 A68 T2-4 B38 A69 T2-5 B38 A69T2-4 B38 A70 T2-5 B38 A70 T2-4 B38 A76 T2-5 B38 A76 T2-4 B38 A77 T2-5B38 A77 T2-4 B38 A78 T2-5 B38 A78 T2-4 B38 A106 T2-5 B38 A106 T2-4 B38A110 T2-5 B38 A110 T5-1 B38 A2 T7-1 B38 A2 T5-1 B38 A5 T7-1 B38 A5 T5-1B38 A35 T7-1 B38 A35 T5-1 B38 A37 T7-1 B38 A37 T5-1 B38 A45 T7-1 B38 A45T5-1 B38 A46 T7-1 B38 A46 T5-1 B38 A49 T7-1 B38 A49 T5-1 B38 A54 T7-1B38 A54 T5-1 B38 A66 T7-1 B38 A66 T5-1 B38 A67 T7-1 B38 A67 T5-1 B38 A68T7-1 B38 A68 T5-1 B38 A69 T7-1 B38 A69 T5-1 B38 A70 T7-1 B38 A70

 

TABLE 41 T5-1 B38 A76 T7-1 B38 A76 T5-1 B38 A77 T7-1 B38 A77 T5-1 B38A78 T7-1 B38 A78 T5-1 B38 A106 T7-1 B38 A106 T5-1 B38 A110 T7-1 B38 A110T1-1 B39 A2 T2-1 B39 A2 T1-1 B39 A5 T2-1 B39 A5 T1-1 B39 A35 T2-1 B39A35 T1-1 B39 A37 T2-1 B39 A37 T1-1 B39 A45 T2-1 B39 A45 T1-1 B39 A46T2-1 B39 A46 T1-1 B39 A49 T2-1 B39 A49 T1-1 B39 A54 T2-1 B39 A54 T1-1B39 A66 T2-1 B39 A66 T1-1 B39 A67 T2-1 B39 A67 T1-1 B39 A68 T2-1 B39 A68T1-1 B39 A69 T2-1 B39 A69 T1-1 B39 A70 T2-1 B39 A70 T1-1 B39 A76 T2-1B39 A76 T1-1 B39 A77 T2-1 B39 A77 T1-1 B39 A78 T2-1 B39 A78 T1-1 B39A106 T2-1 B39 A106 T1-1 B39 A110 T2-1 B39 A110 T2-2 B39 A2 T2-3 B39 A2T2-2 B39 A5 T2-3 B39 A5 T2-2 B39 A35 T2-3 B39 A35 T2-2 B39 A37 T2-3 B39A37 T2-2 B39 A45 T2-3 B39 A45 T2-2 B39 A46 T2-3 B39 A46 T2-2 B39 A49T2-3 B39 A49 T2-2 B39 A54 T2-3 B39 A54 T2-2 B39 A66 T2-3 B39 A66 T2-2B39 A67 T2-3 B39 A67 T2-2 B39 A68 T2-3 B39 A68 T2-2 B39 A69 T2-3 B39 A69T2-2 B39 A70 T2-3 B39 A70 T2-2 B39 A76 T2-3 B39 A76 T2-2 B39 A77 T2-3B39 A77 T2-2 B39 A78 T2-3 B39 A78 T2-2 B39 A106 T2-3 B39 A106 T2-2 B39A110 T2-3 B39 A110 T2-4 B39 A2 T2-5 B39 A2

 

TABLE 42 T2-4 B39 A5 T2-5 B39 A5 T2-4 B39 A35 T2-5 B39 A35 T2-4 B39 A37T2-5 B39 A37 T2-4 B39 A45 T2-5 B39 A45 T2-4 B39 A46 T2-5 B39 A46 T2-4B39 A49 T2-5 B39 A49 T2-4 B39 A54 T2-5 B39 A54 T2-4 B39 A66 T2-5 B39 A66T2-4 B39 A67 T2-5 B39 A67 T2-4 B39 A68 T2-5 B39 A68 T2-4 B39 A69 T2-5B39 A69 T2-4 B39 A70 T2-5 B39 A70 T2-4 B39 A76 T2-5 B39 A76 T2-4 B39 A77T2-5 B39 A77 T2-4 B39 A78 T2-5 B39 A78 T2-4 B39 A106 T2-5 B39 A106 T2-4B39 A110 T2-5 B39 A110 T5-1 B39 A2 T7-1 B39 A2 T5-1 B39 A5 T7-1 B39 A5T5-1 B39 A35 T7-1 B39 A35 T5-1 B39 A37 T7-1 B39 A37 T5-1 B39 A45 T7-1B39 A45 T5-1 B39 A46 T7-1 B39 A46 T5-1 B39 A49 T7-1 B39 A49 T5-1 B39 A54T7-1 B39 A54 T5-1 B39 A66 T7-1 B39 A66 T5-1 B39 A67 T7-1 B39 A67 T5-1B39 A68 T7-1 B39 A68 T5-1 B39 A69 T7-1 B39 A69 T5-1 B39 A70 T7-1 B39 A70T5-1 B39 A76 T7-1 B39 A76 T5-1 B39 A77 T7-1 B39 A77 T5-1 B39 A78 T7-1B39 A78 T5-1 B39 A106 T7-1 B39 A106 T5-1 B39 A110 T7-1 B39 A110 T1-1 B40A2 T2-1 B40 A2 T1-1 B40 A5 T2-1 B40 A5 T1-1 B40 A35 T2-1 B40 A35 T1-1B40 A37 T2-1 B40 A37 T1-1 B40 A45 T2-1 B40 A45 T1-1 B40 A46 T2-1 B40 A46T1-1 B40 A49 T2-1 B40 A49

 

TABLE 43 T1-1 B40 A54 T2-1 B40 A54 T1-1 B40 A66 T2-1 B40 A66 T1-1 B40A67 T2-1 B40 A67 T1-1 B40 A68 T2-1 B40 A68 T1-1 B40 A69 T2-1 B40 A69T1-1 B40 A70 T2-1 B40 A70 T1-1 B40 A76 T2-1 B40 A76 T1-1 B40 A77 T2-1B40 A77 T1-1 B40 A78 T2-1 B40 A78 T1-1 B40 A106 T2-1 B40 A106 T1-1 B40A110 T2-1 B40 A110 T2-2 B40 A2 T2-3 B40 A2 T2-2 B40 A5 T2-3 B40 A5 T2-2B40 A35 T2-3 B40 A35 T2-2 B40 A37 T2-3 B40 A37 T2-2 B40 A45 T2-3 B40 A45T2-2 B40 A46 T2-3 B40 A46 T2-2 B40 A49 T2-3 B40 A49 T2-2 B40 A54 T2-3B40 A54 T2-2 B40 A66 T2-3 B40 A66 T2-2 B40 A67 T2-3 B40 A67 T2-2 B40 A68T2-3 B40 A68 T2-2 B40 A69 T2-3 B40 A69 T2-2 B40 A70 T2-3 B40 A70 T2-2B40 A76 T2-3 B40 A76 T2-2 B40 A77 T2-3 B40 A77 T2-2 B40 A78 T2-3 B40 A78T2-2 B40 A106 T2-3 B40 A106 T2-2 B40 A110 T2-3 B40 A110 T2-4 B40 A2 T2-5B40 A2 T2-4 B40 A5 T2-5 B40 A5 T2-4 B40 A35 T2-5 B40 A35 T2-4 B40 A37T2-5 B40 A37 T2-4 B40 A45 T2-5 B40 A45 T2-4 B40 A46 T2-5 B40 A46 T2-4B40 A49 T2-5 B40 A49 T2-4 B40 A54 T2-5 B40 A54 T2-4 B40 A66 T2-5 B40 A66T2-4 B40 A67 T2-5 B40 A67 T2-4 B40 A68 T2-5 B40 A68 T2-4 B40 A69 T2-5B40 A69 T2-4 B40 A70 T2-5 B40 A70

 

TABLE 44 T2-4 B40 A76 T2-5 B40 A76 T2-4 B40 A77 T2-5 B40 A77 T2-4 B40A78 T2-5 B40 A78 T2-4 B40 A106 T2-5 B40 A106 T2-4 B40 A110 T2-5 B40 A110T5-1 B40 A2 T7-1 B40 A2 T5-1 B40 A5 T7-1 B40 A5 T5-1 B40 A35 T7-1 B40A35 T5-1 B40 A37 T7-1 B40 A37 T5-1 B40 A45 T7-1 B40 A45 T5-1 B40 A46T7-1 B40 A46 T5-1 B40 A49 T7-1 B40 A49 T5-1 B40 A54 T7-1 B40 A54 T5-1B40 A66 T7-1 B40 A66 T5-1 B40 A67 T7-1 B40 A67 T5-1 B40 A68 T7-1 B40 A68T5-1 B40 A69 T7-1 B40 A69 T5-1 B40 A70 T7-1 B40 A70 T5-1 B40 A76 T7-1B40 A76 T5-1 B40 A77 T7-1 B40 A77 T5-1 B40 A78 T7-1 B40 A78 T5-1 B40A106 T7-1 B40 A106 T5-1 B40 A110 T7-1 B40 A110 T1-1 B41 A2 T2-1 B41 A2T1-1 B41 A5 T2-1 B41 A5 T1-1 B41 A35 T2-1 B41 A35 T1-1 B41 A37 T2-1 B41A37 T1-1 B41 A45 T2-1 B41 A45 T1-1 B41 A46 T2-1 B41 A46 T1-1 B41 A49T2-1 B41 A49 T1-1 B41 A54 T2-1 B41 A54 T1-1 B41 A66 T2-1 B41 A66 T1-1B41 A67 T2-1 B41 A67 T1-1 B41 A68 T2-1 B41 A68 T1-1 B41 A69 T2-1 B41 A69T1-1 B41 A70 T2-1 B41 A70 T1-1 B41 A76 T2-1 B41 A76 T1-1 B41 A77 T2-1B41 A77 T1-1 B41 A78 T2-1 B41 A78 T1-1 B41 A106 T2-1 B41 A106 T1-1 B41A110 T2-1 B41 A110

 

TABLE 45 T2-4 B40 A76 T2-5 B40 A76 T2-2 B41 A2 T2-3 B41 A2 T2-2 B41 A5T2-3 B41 A5 T2-2 B41 A35 T2-3 B41 A35 T2-2 B41 A37 T2-3 B41 A37 T2-2 B41A45 T2-3 B41 A45 T2-2 B41 A46 T2-3 B41 A46 T2-2 B41 A49 T2-3 B41 A49T2-2 B41 A54 T2-3 B41 A54 T2-2 B41 A66 T2-3 B41 A66 T2-2 B41 A67 T2-3B41 A67 T2-2 B41 A68 T2-3 B41 A68 T2-2 B41 A69 T2-3 B41 A69 T2-2 B41 A70T2-3 B41 A70 T2-2 B41 A76 T2-3 B41 A76 T2-2 B41 A77 T2-3 B41 A77 T2-2B41 A78 T2-3 B41 A78 T2-2 B41 A106 T2-3 B41 A106 T2-2 B41 A110 T2-3 B41A110 T2-4 B41 A2 T2-5 B41 A2 T2-4 B41 A5 T2-5 B41 A5 T2-4 B41 A35 T2-5B41 A35 T2-4 B41 A37 T2-5 B41 A37 T2-4 B41 A45 T2-5 B41 A45 T2-4 B41 A46T2-5 B41 A46 T2-4 B41 A49 T2-5 B41 A49 T2-4 B41 A54 T2-5 B41 A54 T2-4B41 A66 T2-5 B41 A66 T2-4 B41 A67 T2-5 B41 A67 T2-4 B41 A68 T2-5 B41 A68T2-4 B41 A69 T2-5 B41 A69 T2-4 B41 A70 T2-5 B41 A70 T2-4 B41 A76 T2-5B41 A76 T2-4 B41 A77 T2-5 B41 A77 T2-4 B41 A78 T2-5 B41 A78 T2-4 B41A106 T2-5 B41 A106 T2-4 B41 A110 T2-5 B41 A110 T5-1 B41 A2 T7-1 B41 A2T5-1 B41 A5 T7-1 B41 A5 T5-1 B41 A35 T7-1 B41 A35 T5-1 B41 A37 T7-1 B41A37 T5-1 B41 A45 T7-1 B41 A45 T5-1 B41 A46 T7-1 B41 A46

 

TABLE 46 T5-1 B41 A49 T7-1 B41 A49 T5-1 B41 A54 T7-1 B41 A54 T5-1 B41A66 T7-1 B41 A66 T5-1 B41 A67 T7-1 B41 A67 T5-1 B41 A68 T7-1 B41 A68T5-1 B41 A69 T7-1 B41 A69 T5-1 B41 A70 T7-1 B41 A70 T5-1 B41 A76 T7-1B41 A76 T5-1 B41 A77 T7-1 B41 A77 T5-1 B41 A78 T7-1 B41 A78 T5-1 B41A106 T7-1 B41 A106 T5-1 B41 A110 T7-1 B41 A110 T1-1 B42 A2 T2-1 B42 A2T1-1 B42 A5 T2-1 B42 A5 T1-1 B42 A35 T2-1 B42 A35 T1-1 B42 A37 T2-1 B42A37 T1-1 B42 A45 T2-1 B42 A45 T1-1 B42 A46 T2-1 B42 A46 T1-1 B42 A49T2-1 B42 A49 T1-1 B42 A54 T2-1 B42 A54 T1-1 B42 A66 T2-1 B42 A66 T1-1B42 A67 T2-1 B42 A67 T1-1 B42 A68 T2-1 B42 A68 T1-1 B42 A69 T2-1 B42 A69T1-1 B42 A70 T2-1 B42 A70 T1-1 B42 A76 T2-1 B42 A76 T1-1 B42 A77 T2-1B42 A77 T1-1 B42 A78 T2-1 B42 A78 T1-1 B42 A106 T2-1 B42 A106 T1-1 B42A110 T2-1 B42 A110 T2-2 B42 A2 T2-3 B42 A2 T2-2 B42 A5 T2-3 B42 A5 T2-2B42 A35 T2-3 B42 A35 T2-2 B42 A37 T2-3 B42 A37 T2-2 B42 A45 T2-3 B42 A45T2-2 B42 A46 T2-3 B42 A46 T2-2 B42 A49 T2-3 B42 A49 T2-2 B42 A54 T2-3B42 A54 T2-2 B42 A66 T2-3 B42 A66 T2-2 B42 A67 T2-3 B42 A67 T2-2 B42 A68T2-3 B42 A68 T2-2 B42 A69 T2-3 B42 A69

 

TABLE 47 T2-2 B42 A70 T2-3 B42 A70 T2-2 B42 A76 T2-3 B42 A76 T2-2 B42A77 T2-3 B42 A77 T2-2 B42 A78 T2-3 B42 A78 T2-2 B42 A106 T2-3 B42 A106T2-2 B42 A110 T2-3 B42 A110 T2-4 B42 A2 T2-5 B42 A2 T2-4 B42 A5 T2-5 B42A5 T2-4 B42 A35 T2-5 B42 A35 T2-4 B42 A37 T2-5 B42 A37 T2-4 B42 A45 T2-5B42 A45 T2-4 B42 A46 T2-5 B42 A46 T2-4 B42 A49 T2-5 B42 A49 T2-4 B42 A54T2-5 B42 A54 T2-4 B42 A66 T2-5 B42 A66 T2-4 B42 A67 T2-5 B42 A67 T2-4B42 A68 T2-5 B42 A68 T2-4 B42 A69 T2-5 B42 A69 T2-4 B42 A70 T2-5 B42 A70T2-4 B42 A76 T2-5 B42 A76 T2-4 B42 A77 T2-5 B42 A77 T2-4 B42 A78 T2-5B42 A78 T2-4 B42 A106 T2-5 B42 A106 T2-4 B42 A110 T2-5 B42 A110 T5-1 B42A2 T7-1 B42 A2 T5-1 B42 A5 T7-1 B42 A5 T5-1 B42 A35 T7-1 B42 A35 T5-1B42 A37 T7-1 B42 A37 T5-1 B42 A45 T7-1 B42 A45 T5-1 B42 A46 T7-1 B42 A46T5-1 B42 A49 T7- 1 B42 A49 T5-1 B42 A54 T7-1 B42 A54 T5-1 B42 A66 T7-1B42 A66 T5-1 B42 A67 T7-1 B42 A67 T5-1 B42 A68 T7-1 B42 A68 T5-1 B42 A69T7-1 B42 A69 T5-1 B42 A70 T7-1 B42 A70 T5-1 B42 A76 T7-1 B42 A76 T5-1B42 A77 T7-1 B42 A77 T5-1 B42 A78 T7-1 B42 A78 T5-1 B42 A106 T7-1 B42A106 T5-1 B42 A110 T7-1 B42 A110

 

TABLE 48 T1-1 B43 A2 T2-1 B43 A2 T1-1 B43 A5 T2-1 B43 A5 T1-1 B43 A35T2-1 B43 A35 T1-1 B43 A37 T2-1 B43 A37 T1-1 B43 A45 T2-1 B43 A45 T1-1B43 A46 T2-1 B43 A46 T1-1 B43 A49 T2-1 B43 A49 T1-1 B43 A54 T2-1 B43 A54T1-1 B43 A66 T2-1 B43 A66 T1-1 B43 A67 T2-1 B43 A67 T1-1 B43 A68 T2-1B43 A68 T1-1 B43 A69 T2-1 B43 A69 T1-1 B43 A70 T2-1 B43 A70 T1-1 B43 A76T2-1 B43 A76 T1-1 B43 A77 T2-1 B43 A77 T1-1 B43 A78 T2-1 B43 A78 T1-1B43 A106 T2-1 B43 A106 T1-1 B43 A110 T2-1 B43 A110 T2-2 B43 A2 T2-3 B43A2 T2-2 B43 A5 T2-3 B43 A5 T2-2 B43 A35 T2-3 B43 A35 T2-2 B43 A37 T2-3B43 A37 T2-2 B43 B45 T2-3 B43 A45 T2-2 B43 A46 T2-3 B43 A46 T2-2 B43 A49T2-3 B43 A49 T2-2 B43 A54 T2-3 B43 A54 T2-2 B43 A66 T2-3 B43 A66 T2-2B43 A67 T2-3 B43 A67 T2-2 B43 A68 T2-3 B43 A68 T2-2 B43 A69 T2-3 B43 A69T2-2 B43 A70 T2-3 B43 A70 T2-2 B43 A76 T2-3 B43 A76 T2-2 B43 A77 T2-3B43 A77 T2-2 B43 A78 T2-3 B43 A78 T2-2 B43 A106 T2-3 B43 A106 T2-2 B43A110 T2-3 B43 A110 T2-4 B43 A2 T2-5 B43 A2 T2-4 B43 A5 T2-5 B43 A5 T2-4B43 A35 T2-5 B43 A35 T2-4 B43 A37 T2-5 B43 A37 T2-4 B43 A45 T2-5 B43 A45T2-4 B43 A46 T2-5 B43 A46

 

TABLE 49 T2-4 B43 A49 T2-5 B43 A49 T2-4 B43 A54 T2-5 B43 A54 T2-4 B43A66 T2-5 B43 A66 T2-4 B43 A67 T2-5 B43 A67 T2-4 B43 A68 T2-5 B43 A68T2-4 B43 A69 T2-5 B43 A69 T2-4 B43 A70 T2-5 B43 A70 T2-4 B43 A76 T2-5B43 A76 T2-4 B43 A77 T2-5 B43 A77 T2-4 B43 A78 T2-5 B43 A78 T2-4 B43A106 T2-5 B43 A106 T2-4 B43 A110 T2-5 B43 A110 T5-1 B43 A2 T7-1 B43 A2T5-1 B43 A5 T7-1 B43 A5 T5-1 B43 A35 T7-1 B43 A35 T5-1 B43 A37 T7-1 B43A37 T5-1 B43 A45 T7-1 B43 A45 T5-1 B43 A46 T7-1 B43 A46 T5-1 B43 A49T7-1 B43 A49 T5-1 B43 A54 T7-1 B43 A54 T5-1 B43 A66 T7-1 B43 A66 T5-1B43 A67 T7-1 B43 A67 T5-1 B43 A68 T7-1 B43 A68 T5-1 B43 A69 T7-1 B43 A69T5-1 B43 A70 T7-1 B43 A70 T5-1 B43 A76 T7-1 B43 A76 T5-1 B43 A77 T7-1B43 A77 T5-1 B43 A78 T7-1 B43 A78 T5-1 B43 A106 T7-1 B43 A106 T5-1 B43A110 T7-1 B43 A110

 

Furthermore, the compounds having the above-mentioned structure wherein—X′—Y′ is one selected from a group of OCH₂CH═CMe₂, OCH₂-2-furyl,OCH₂-3-furyl, OCH₂C≡CMe, NHCH₂CH═CMe₂, N(iPr)SO₂NHMe, NHCH(Me)CH₂OMe,NHiPr, NH-iBu, NHc-Pent, NHCH₂c-Hex, NHc-Hex, NHc-Hex-4-(═NOMe),NHcHex-4, 4-(OMe)₂, NHCH₂C₆H₄-4-B(OH)₂, NHCH₂C₆H₄-2-OH,NHCH₂C₆H₃-3,4-(OH)₂, NHCH₂C₆H₂-3, 4, 5-(OMe)₃, NHCH₂C₆H₄-4-COOH,NHCH₂C₆H₄-4-OH, NHCH₂C₆H₄-3-OH, NHCH₂-2-furyl, NHCH₂-3-furyl,NH-4-tetrahydropyran, NHCH₂-benzopyrrolyl, NHCH₂-2-thiazolyl,NHCH₂-quinolyl, NHcHex-4, 4-ethylenedioxy, 1-pyrolidinyl, 4-morpholinyl,1-piperadinyl, 4-thiomorpholinyl, 1-piperidyl,

 

are preferable. The compounds wherein —X′—Y′ is —OCH₂-2-furyl,—NHCH₂CH═CMe₂ or —OCH₂CH═CMe₂ are more preferable.

A process for producing the compound (I) is as follows.

A Process for Producing the Compound (I′)

A compound of the following formula (I′) (hereinafter referred to as “acompound (I′)”) can be produced by reacting a compound of the formula(IIa) (hereinafter referred to as “a compound (IIa)”) with a bicycliccompound of the formula (IIIa) (hereinafter referred to as “a compound(IIIa)”) or by reacting a compound of the formula (IIb) (hereinafterreferred to as “a compound (IIb)”) with a bicyclic compound of theformula (IIIb) (hereinafter referred to as “a compound (IIIb)”).

 

wherein either of L and Z is dihydroxyborane, di(lower)alkyl borane ordi(lower) alkoxyborane and the other is halogen or —OSO₂(C_(q)F_(2q+1))(q is an integer of 0 to 4) and other symbols are the same as definedabove.

The compound (I′) can be produced by reacting the compound (Ia) with thecompound (IIIa) or by reacting the compound (IIb) with the compound(IIIb) in a mixture of an appropriate solvent such as benzene, toluene,N, N-dimethylformamide, dimethoxyethane, tetrahydrofuran, dioxane,ethanol, methanol or the like and water or in an anhydrous solution inthe presence of a palladium catalyst such as Pd(PPh₃)₄, PdCl₂(PPh₃)₂,PdCl₂(OAc)₂, PdCl₂(CH₃CN)₂ or the like, preferably Pd(PPh₃)₄, under abasic condition (for example, by K₃PO₄, NaHCO₃, NaOEt, Na₂CO₃, Et₄NCl,Ba(OH)₂, Cs₂CO₃, CsF, NaOH, Ag₂CO₃ or the like) at room temperature orwith heating for several tens minutes to several tens hours.

One of substituents L and Z of the compounds to be reacted may be any ofthe borane groups which are applicable in the Suzuki Reaction (ChemicalCommunication 1979, 866, Journal of Synthetic Organic Chemistry, Japan,1993, Vol.51, No.11, 91-100) and dihydroxyborane is preferable. Theother may be any of the leaving groups which are applicable in theSuzuki Reaction, for example, halogen, —OSO₂(C_(q)F_(2q+1)) wherein q isan integer of 0 to 4, or the like. Specifically, halogen,trifluoromethanesulfonyloxy (hereinafter referred to as OTf) or the likeis preferable and bromine, iodine or OTf is more preferable.

The other substituents of A ring, B ring and C ring and —X—Y of thecompounds (IIa), (IIIa), (IIb) and (IIIb) may be any of the groups whichdo not affect the Suzuki Reaction, for example, any groups other thanhalogen and —OSO₂(C_(q)F_(2q+1)) wherein q is an integer of 0 to 4.

For example, Y may be optionally substituted lower alkyl, optionallysubstituted lower alkenyl, optionally substituted lower alkynyl,optionally substituted acyl, optionally substituted cycloalkyl,optionally substituted cycloalkenyl, optionally substituted aryl oroptionally substituted 5- or 6-membered heterocycle which may be fusedwith benzene ring, Y may be optionally substituted lower alkoxy when Xis —CH₂— and Y may be optionally substituted lower alkoxycarbonyl,optionally substituted lower alkylsulfonyl or optionally substitutedarylsulfonyl when X is —O— or —NR¹—.

Even if any substituent of A ring, B ring or C ring is halogen, thesereactions can be carried out without difficulty when the reactivity ofthe substituent L with the substituent Z is higher than that of halogenwith either of substituents L and Z.

Even if either of substituents of A ring, B ring and C ring or —X—Y ishydroxy, the above reactions can be preferably carried out. Preferablythe above reactions may be carried out after the protection of hydroxygroup with a usual hydroxy-protecting group such as methoxymethyl,benzyl, tert-butyldimethylsilyl, methanesulfonyl, p-toluenesulfonyl orthe like, followed by deprotection by the usual methods.

As processes for producing the compound (I′), the above mentioned SuzukiReaction is most preferable in view of the efficiency and easiness butsilicon, zinc, tin or the like can be used in place of the borane groupin the above scheme.

For example, in the case that one of A and Z is —SiR¹⁷ _(3-r)(Hal)_(r)wherein R¹⁷ are independently lower alkyl, Hal is halogen and r is aninteger of 1 to 3 and the other is halogen or —OSO₂(C_(q)F_(2q+1))wherein q is an integer of 0 to 4, the coupling reaction may be carriedout using a usual palladium catalyst (Synlett (1991) 845-853, J. Org.Chem. 1996, 61, 7232-7233). Examples of preferable palladium catalystsare (i-Pr₃P)₂PdCl₂, [(dcpe)PdCl₂](dcpe=Cy₂PCH₂CH₂PCy₂), (η³-C₃H₅PdCl)₂and the like.

Even in the case that one of L and Z is —SnR¹⁸ ₃ wherein R¹⁸ are eachindependently lower alkyl and the other is halogen, acetyloxy or—OSO₂(C_(q)F_(2q+1)) wherein q is an integer of 0 to 4, an objectivecompound can be obtained using a usual palladium catalyst (preferablyPd(PPh₃)₄ or the like) (Angew. Chem. Int. Ed. Engl. 25 (1986) 508-524).

In the case that one of L and Z is —Zn(Hal) wherein Hal is halogen andthe other is halogen, an objective compound can be obtained (Acc, Chem.Res. 1982, 15, 340-348). Any usual palladium catalyst is applicable andPd(PPh₃)₄, PdCl₂(dppf), PdCl₂(PPh₃)₂, PdCl₂(P(o-Tolyl)₃)₂, Pd(OAc)₂ andthe like are exemplified as preferable examples.

All of these reactions may be carried out in a suitable solvent such asN,N-dimethylformamide, tetrahydrofuran or the like at room temperatureor with heating for several tens minutes to several tens hours.

As compound (IIIa) and (IIIb) in the above reactions, may be used knowncompounds or compounds which are derived from a compound of thefollowing formula (Va) (hereinafter referred to as “a compound (Va)”) orthe following formula (Vb) (hereinafter referred to as “a compound(Vb)”) which can be produced by the known method or the followingmethod.

 

wherein D is any of the groups which do not affect the Suzuki Reactionof L with Z, and may be the same group as L when a compound of theformula (IVb) is a bisymmetric compound. The other symbols are the sameas above.

The compound (IIb) is reacted with the compound (IVa) or the compound(IIa) is reacted with (IVb) to give the compound (Va) or (Vb). When thecompound (IVa) or (IVb) is not a bisymmetric compound, D is preferably agroup which does not affect the Suzuki Reaction of L with Z and can beeasily converted to L. For example, hydroxy, hydrogen, formyl, nitro orthe like is preferable. In the reaction of L with Z, silicon, zinc, tinor the like can be used in place of the borane group as mentioned above.

D is converted into a group L which is applicable to the SuzukiReaction.

A compound wherein D is hydroxy may be reacted with atrifluoromethanesulfonating agent such as trifluoromethanesulfonicanhydride, trifluoromethansulfonyl chloride,N-phenyltrifluorometbanesulfone imide or the like in a suitable solventsuch as dichloromethane, chloroform, tetrahydrofuran or benzene in thepresence of a base such as sodium hydride, pyridine, triethylamine,potassium carbonate or the like at −20° C. or with heating for severalminutes to several tens hours to give an objective compound wherein L isOTf.

For example, a compound wherein D is hydrogen may be reacted with ahalogenating agent such as bromine, chlorine, iodine, N-bromosuccinimideor the like in a suitable solvent such as acetic acid, dichloromethane,chloroform, carbon tetrachloride, benzene, water or the like at −20° C.or with heating for several minutes to several tens hours to give anobjective compound wherein L is halogen.

A compound wherein D is formyl may be oxidated by the Baeyer-Villigerreaction to give a compound wherein D is formyloxy, followed byhydrolysis to give a compound wherein D is hydroxy. The compound whereinL is OTf can be obtained by the similar process as mentioned above.

A compound wherein D is nitro may be reduced to give a compound whereinD is amino, followed by the Sandmeyer Reaction to give a compound L ishalogen.

A Process for Producing the Compound (I″)

A compound of the following formula (I″) (hereinafter referred to as “acompound (I″)”) can be produced by the Suzuki Reaction of a compound ofthe formula (VI) (hereinafter referred to as “a compound (VI)”) with acompound of the formula (IIa) (hereinafter referred to as “a compound(IIa)”) or by condensation of a compound of the formula (VII)(hereinafter referred to as “a compound (VII)”) with a compound of theformula (VIII) (hereinafter referred to as “a compound (VIII)”)

 

wherein either of M and Q is hydroxy or amino and the other is halogen,lower alkylsulfonyloxy, arylsulfonyloxy, lower alkylsulfonyl,arylsulfonyl or methyl having them as substituents, either of M and Q islithium or Mg(Hal) wherein Hal is halogen and the other is carboxy,lower alkoxycarbonyl, carbamoyl or formyl, either of M and Q is formyland the other is halogenomethyl, or either of M and Q is ethynyl and theother is halogen; and the other symbols are the same as defined above.

Various conditions for a reaction of the compound (VI) with the compound(IIa) are the same as those for the process for producing the compound(I′).

In a reaction of the compound (VII) with a compound (VIII), when V² ofan objective compound is —O—, —NH—, —OCH₂—, —CH₂O— or —NHCH₂—, either ofM and Q is hydroxy or amino and the other is a leaving group such ashalogen, lower alkylsulfonyloxy, arylsulfonyloxy, lower alkylsulfonyl,arylsulfonyl or the like or methyl having the leaving group assubstituents. These two compounds are reacted in a suitable solvent suchas benzene, toluene, acetone, acetonitrile, N,N-dimethylformamide,dimethylsulfoxide, pyridine, methanol, ethanol or the like in thepresence of a base such as sodium hydride, pyridine, triethylamine,potassium carbonate, sodium hydroxide, potassium hydroxide or the like,if necessary by adding a copper catalyst such as copper powder, CuCl,CuO or the like at 0° C. or with heating for several minutes to severaltens hours to give the objective compound.

In a reaction of the compound (VII) with the compound (VIII), when V² ofan objective compound is —CO— or —CH(OH)—, either of M and Q is anorganic metal such as lithium or Mg(Hal) wherein Hal is halogen and theother is carboxy, lower alkoxycarbonyl, carbamoyl or formyl. These twocompounds are reacted in a suitable solvent such as diethylether,tetrahydrofuran, dimethoxyethan, dioxane or the like at −78° C. to withheating for several minutes to several hours to give an objectivecompound.

When V² of an objective compound is —CH(OR)— wherein R is lower alkyl,after a compound wherein V² is —CH(OH)— is obtained, the obtainedcompound may be subjected to alkylation.

A compound wherein V² is —CO— may be obtained by reacting a compoundwherein V² is —CH(OH)— with an oxidizing agent such as chromicanhydride, Jone's reagent or the like in a solvent such ast-butylalcohol, acetone or the like depending on the oxidizing agent at0° C. or with heating for several hours. A compound wherein V² is—CH(OH)— can be obtained also by reacting a compound wherein V² is —CO—with an reducing agent such as sodium borohydride, aluminium lithiumhydride or the like in a suitable solvent such as diethyl ether,tetrahydrofuran, dimethoxyethane, dioxane, methanol, ethanol or thelike.

When a compound wherein V² of an objective compound is —CH═CH—, eitherof M and Q is formyl and the other is halogenomethyl (for example,halogen is chloro, bromo or iodo). An objective compound can be obtainedby the Wittig Reaction (Organic Reaction, vol.14, p. 270, 1965).

When V² of an objective compound is —CH≡CH—, either of M and Q isethynyl and the other is halogen (preferably bromo or iodo). Theobjective compound can be synthesized by a coupling reaction with agenerally used palladium catalyst (for example, Synthesis. (1980) 627,Tetrahedron, 1982, 38, 631).

Other substituents of A ring, B ring, C ring and —X—Y of the compound(VI), (IIa), (VII) and (VIII) may be any substituent which does notaffect the Suzuki Reaction of L with Z or a condensing reaction of Mwith Q. Even if in a reaction of the compound (VI) with the compound(IIa) wherein either of substituents is halogen, this reaction may becarried out without difficulty if the reactivity of a substituent L witha substituent Z is higher than the reactivity with halogen. Even ifeither of substituents is hydroxy, the above reaction can be carriedout. Preferably hydroxy is previously protected, followed a deprotectionafter the above reaction.

As the compound (VI) in the above scheme, it may be used a knowncompound or a compound of the formula (X) which is synthesized in thefollowing method.

 

wherein D′ is a group which does not affect a condensing reaction of Mwith Q and when a compound of the formula (IX) is a symmetric compound,D′ may be the same group as Q, and the other symbols are the same asdefined above.

When the compound (IX) is not a symmetric compound, D′ is preferably agroup which does not affect the condensing reaction of M with Q andwhich can easily be converted to L. For example, hydrogen, formyl,protected hydroxy, nitro or the like is preferable. As ahydroxy-protecting group, exemplified are benzyl, t-butyldimethylsilyl,methoxymethyl and the like. A method for converting D′ to L is similarto the above method for converting D to L. Other various conditions aresimilar to that for reacting the compound (VII) with the compound(VIII).

A known compound may be used as a compound (VIII) in the above reactionscheme and a compound synthesized by the usual method or derived fromthe above compound (Vb) by the usual method also may be used.

In the case that a compound has a substituent interfering of the abovereaction, the substituent may be protected with a suitable protectinggroup in advance and the protecting group may be removed in a suitablestep by the usual method. For example, if hydroxy interferes thereaction, it may be protected with methoxymethyl, methanesulfonyl,benzyl, trifluoromethanesulfonyl, tert-butyldimethylsilyl or the like,followed by deprotection in a suitable step.

For example, for a protection of hydroxy with methanesulfonyl, acompound which has hydroxy may be reacted with methanesulfonyl chloridein a solvent such as dichloromethane, chloroform, carbon tetrachlorideor the like in the presence of a base such as triethylamine, pyridine orthe like under ice-cooling or at room temperature for several hours. Theprotected compound may be deprotected with 1-4 N sodium hydroxide,potassium hydroxide, aqueous solution thereof, sodium methoxide, ethylmagnesium bromide or the like in a solvent such as dimethylsulfoxide,dimethylformamide, tetrahydrofuran, dioxane, dimethoxyethane or the likeat room temperature or with heating for several tens minutes to severalhours.

When methoxymethyl is used as a hydroxy-protecting group, a compoundwhich has hydroxy may be reacted with chloromethylmethylether in asolvent such as tetrahydrofuran, dioxane, dimethoxyethane or the like inthe presence of sodium hydride, diisopropylethylamine or the like togive a compound which has a protected hydroxy group. The compound may besubjected to a usual deprotection reaction with hydrochloric acid,sulfuric acid or the like in a solvent such as methanol,tetrahydrofuran, acetic acid or the like for a deprotection.

When tert-butyldimethylsilyl is used as a protecting group, a compoundwhich has hydroxy may be reacted with tert-butyldimethylsilyl chloride,tert-butyldimethylsilyl triflate or the like in a solvent such asdimethylformamide, acetonitrile, tetrahydrofuran, dimethylformamide,dichloromethane or the like in the presence of imidazole, triethylamine,2,6-lutidine or the like. For a deprotection reaction the protectedcompound may be reacted with tetrabutylammonium fluoride or the like ina solvent such as tetrahydrofuran or the like.

A compound of the present invention thus obtained can be converted intoa prodrug thereof. The term “prodrug” includes compounds which caneasily be converted to the compound having the activity of the presentinvention in a living body. Any usual method for conversion into aprodrug may be used.

For example, hydroxy or amino which is attached to any possible positionof a compound of the present invention may be substituted with a usualgroup for manufacturing a prodrug. For example, substituted acyl(wherein the substituent is carboxy, sulfo, amino, lower alkylamino orthe like), phosphonoxy or the like may be introduced into the hydroxy,and substituted alkoxycarbonyl (wherein the substituent is halogen,acyloxy, hydroxyacyloxy, carboxyacyloxy, heterocyclylcarbonyloxy or thelike) or substituted alkyl (wherein the substituent is aroylamino whichmay be substituted with acyloxy(lower)alkoxy or the like) may beintroduced into the amino.

More definitely, when A ring or C ring has hydroxy as a substituent, asubstituent such as —COCH₂CH₂COOH, —COCH═CHCOOH, —COCH₂SO₃H, —PO₃H₂,—COCH₂NMe₂, —CO-Py wherein Py is pyridine or the like may be introduced.When A ring or C ring has amino as a substituent(e.g., X, X′ or thelike), —COOCH₂O(C═O)CH₂OH, —COOCH₂O(C═O)CH₂CH₂COOH, —COOCH₂OAc,—COOCH(Me)OAc, —COOCH(Me)OCOCMe₃, —COOCH₂OCO(CH₂)₁₄Me, —COOCH₂OCO-Pyr,—CH₂NHCO-C₆H₄-o-OCH₂OAc or the like may be introduced.

The immunosuppressant or anti-allergic agent of the present invention isuseful for prevention or treatment of allergic diseases such asrejection symptom against transplantation of an organ or a tissue,graft-versus-host reaction caused by bone marrow transplantation, atopicallergic diseases (for example, bronchial asthma, allergic rhinitis,allergic dermatitis and the like), hypereosinophils syndrome, allergicconjunctivitis, systemic lupus erythematosus, polymyositis,dermatomyositis, scleriasis, MCTD, chronic rheumatoid arthritis,inflammatory bowel disease, injury caused by ischemia-reperfusion,pollenosis, allergic rhinitis, urticaria, psoriasis and the like.

A compound of the present invention can be administered orally orparenterally as a immunosuppressant, anti-allergic agent and/orsuppressant on the IgE production. In the case of oral administration,it may be in any usual form such as tablets, granules, powders,capsules, pills, solutions, syrups, buccal tablets, sublingual tabletsand the like. When the compound is parenterally administered, any usualform is preferable, for example, injections (e.g., intravenous,intramuscular), suppositories, endermic agents, vapors and the like.Oral administration is particularly preferable.

A pharmaceutical composition may be manufactured by mixing an effectiveamount of a compound of the present invention with variouspharmaceutical ingredients suitable for the administration form, such asexcipients, binders, moistening agents, disintegrators, lubricants,diluents and the like. When the composition is of an injection, anactive ingredient can be sterilized with a suitable carrier to give apharmaceutical composition.

Specifically, examples of the excipients include lactose, saccharose,glucose, starch, calcium carbonate, crystalline cellulose and the like,examples of the binders include methylcellulose, carboxymethylcellulose,hydroxypropylcellulose, gelatin, polyvinylpyrrolidone and the like,examples of the disintegrators include carboxymethylcellulose, sodiumcarboxymethylcellulose, starch, sodium alginate, agar, sodium laurylsulfate and the like, and examples of the lubricants include talc,magnesium stearate, macrogol and the like. Cacao oil, macrogol, methylcellulose and the like may be used as base materials of suppositories.When the composition is manufactured as solutions, emulsified injectionsor suspended injections, dissolving accelerators, suspending agents,emulsifiers, stabilizers, preservatives, isotonic agents and the likemay be added. For oral administration, sweetening agents, flavors andthe like may be added.

Although the dosage of a compound of the present invention as animmunosuppressant, anti-allergic agent and/or suppressant on the IgEproduction should be determined in consideration of the patient's ageand body weight, the type and degree of diseases, the administrationroute or the like, a usual oral dosage for human adults is 0.05-100mg/kg/day and preferable is 0.1-10 mg/kg/day. For parenteraladministration, although the dosage highly varies with administrationroutes, a usual dosage is 0.005-10 mg/kg/day, preferably, 0.01-1mg/kg/day. The dosage may be administered in one or several divisionsper day.

The present invention is further explained by the following Examples andExperiments, which are not intended to limit the scope of the presentinvention.

EXAMPLE

The abbreviations used in EXAMPLE mean the following.

Ac acetyl Bn benzyl Et ethyl ^(i)Pr isopropyl Me methyl Msmethanesulfonyl Ph phenyl Py pyridyl TBS tert-butyldimethylsilyl TFAAtrifluoroacetic anhydride THF tetrahydrofuran

 

Example 1 Synthesis of Compounds (Ia-71), (Ia-73, (Ia-75) and (Ia-76)

 

(Step 1) Synthesis of Compound (2)

To a solution of 831 mg (2.32 mmol) of compound (1) (WO98/04508,Reference Example 1) in 12 ml of toluene were added 701 mg (2.79 mmol)of 2, 5-dibromo-3-methylpyridine, 80 mg (0.07 mmol) oftetrakis(triphenylphosphin)palladium (0), and 6 ml of an aqueoussolution of 2 M sodium carbonate at room temperature. The mixture washeated refluxed under a nitrogen atmosphere for 4 hours. After cooling,the mixture was diluted with water and extracted with ethyl acetate. Theextract was washed with saturated brine, dried and concentrated. Theresidue was purified by silica gel chromatography (hexane-ethyl 97:3) togive compound (2) (808 mg; 60% yield).

(Step 2) Synthesis of Compound (4)

According to the method of Step 1, 404 mg (0.83 mmol) of compound (2)was reacted with 231 mg (0.92 mmol) of boronic acid (3) (GB 2276162 A)to give compound (4) (411 mg; 81% yield).

(Step 3) Synthesis of Compound (Ia-71)

To a solution of 411 mg (0.67 mmol) of compound (4) in 3.4 ml oftetrahydrofuran was added a solution of 1 M tetrabutyl ammonium fluoridein 1.4 ml (1.40 mmol) of tetrahydrofuran and the mixture was stirred for3 hours. The solution was poured into an aqueous solution of 5%potassium hydrogen sulfate and extracted with ethyl acetate. The extractwas washed with saturated brine, dried and concentrated. The residue wascrystallized from ethyl acetate to give compound (Ia-71) (247 mg; 96%yield).

(Step 4) Synthesis of Compound (Ia-75)

To a solution of 227 mg (0.59 mmol) of compound (Ia-71) in 3 ml oftetrahydrofuran were added 0.17 ml (1.18 mmol) of triethylamine and 0.07ml (0.89 mmol) of methanesulfonyl chloride successively and the mixturewas stirred for 20 hours at room temperature. The solution was dilutedwith ethyl acetate, washed with water, 5% aqueous solution of sodiumhydrogencarbonate and saturated saline successively, dried andconcentrated. The residue was crystallized from hexane-ethyl acetate togive compound (Ia-75) (303 mg; 95% yield).

(Step 5) Synthesis of Compound (5)

To a solution of 283 mg (0.52 mmol) of compound (Ia-75) in 2.6 ml ofdichloromethane was added a solution of 1 M boron tribromide in 0.63 ml(0.63 mmol) of dichloromethane at −78° C. and the mixture was stirredfor an hour at the same temperature. After the excessive reagent wasdecomposed by addition of methanol, the solution was poured into 5%aqueous solution of sodium hydrogencarbonate and extracted with ethylacetate. The extract was washed with saturated brine, dried andconcentrated. The residue was crystallized from hexane-ethyl acetate togive compound (5) (204 mg; 87% yield).

(Step 6) Synthesis of Compound (Ia-76)

To a solution of 184 mg (0.41 mmol) of compound (5) in 2 ml of acetonewere added 169 mg (1.23 mmol) of potassium carbonate and 0.12 ml (1.02mmol) of prenyl bromide successively and the mixture was stirred for 14hours at room temperature. The solution was diluted ethyl acetate,washed with water and saturated brine successively, dried andconcentrated. The residue was purified by silica gel chromatography(hexane-ethyl acetate 1:1) and crystallized from hexane-ethyl acetate togive compound (Ia-76) (170 mg; 80% yield).

(Step 7) Synthesis of Compound (Ia-73)

To a solution of 149 mg (0.29 mmol) of compound (Ia-76) in 1.4 ml oftetrahydrofuran was added a solution of 28% sodium methoxide in 0.6 ml(2.89 mmol) of methanol under ice-cooling and the mixture was stirred atroom temperature for 17 hours. The solution was poured into 5% aqueoussolution of ammonium chloride and extracted with ethyl acetate. Theextract was washed with saturated brine, dried and concentrated. Afterthe residue was purified by silica gel chromatography (hexane-ethyl7:3), the obtained product was crystallized from diethylether-hexane togive compound (Ia-73) (88mg; 84 % yield).

Example 2 Synthesis of Compounds (Ib-15), (Ib-37) and (Ib-49)

 

(Step 1) Synthesis of Compound (Ib-49)

According to the method of Example 1 Step 1, 200 mg (0.74 mmol) ofboronic acid (6) was reacted with 236 mg (1.49 mmol) of2-chloro-5-nitropyridine to give compound (Ib-49) (232 mg; 90% yield).

(Step 2) Synthesis of Compound (Ib-15)

To a solution of 257 mg (0.74 mmol) of compound (Ib-49) in 5 ml oftoluene were added 5 ml of water, 207 mg (3.70 mmol) of iron powder and213 mg (3.70 mmol) of ammonium chloride and the mixture was refluxed for15 hours. After cooling, insoluble material was filtered off withcelite. The filtrate was extracted with ethyl acetate and the extractwas washed with saturated brine, dried and concentrated. After theresidue was purified by silica gel chromatography (hexane-ethyl acetate1:3), the obtained product was crystallized from ethyl acetate to givecompound (Ib-15) (161 mg; 69% yield).

(Step 3) Synthesis of Compound (Ib-37)

To a solution of 130 mg (0.41 mmol) of compound (Ib-15) in 4 ml ofdichloromethane were added 0.05 ml (0.61 mmol) of pyridine and 86 mg(0.49 mmol) of methanesulfonic anhydride under ice-cooling and themixture was stirred for an hour. The solution was diluted with ethylacetate, washed with water, 5% aqueous solution of sodiumhydrogencarbonate and saturated brine successively, dried andconcentrated. The residue was crystallized from ethyl acetate to givecompound (Ib-37) (124 mg; 77% yield).

Example 3 Synthesis of Compounds of (Ib-11), (Ib-12), (Ib-16), (Ib-21),(Ib-46) and (Ib-47)

 

(Step 1) Synthesis of Compound (Ib-46)

To a mixture of a solution of 867 mg (1.36 mmol) of compound (7)(WO98/04508, Reference Examples 4 and 6) in 16 ml of 1,2-dimethoxyethane and 5 ml of ethanol were added 200 mg (1.26 mmol) of2-chloro-5-nitropyridine, 44 mg(0.04 mmol) oftetrakis(triphenylphosphine)palladium (0) and 5 ml of aqueous solutionof 2 M sodium carbonate at room temperature and the solution wasrefluxed under a nitrogen atmosphere for 3 hours. After cooling, themixture was diluted with water and extracted with ethyl acetate. Theextract was washed with saturated brine, dried, concentrated and theobtained residue was dissolved in 6 ml of tetrahydrofuran. To thesolution was added a solution of 1 M tetrabutylammonium fluoride in 2 ml(2.02 mmol) of tetrahydrofuran under ice-cooling and the mixture wasstirred for 1.5 hours. After the solution was poured into water andextracted with ethyl acetate, the extract was washed with saturatedbrine, dried and concentrated. The residue was purified by silica gelchromatography (hexane-ethyl acetate 7:3) and crystallized fromhexane-ethyl acetate to give compound (Ib-46) (472 mg; 79% yield).

(Step 2) Synthesis of Compound (Ib-47)

According to the method of Example 1 Step 4, a solution of 458 mg (0.97mmol) of compound (Ib-46) in 4.8 ml of tetrahydrofuran was treated with0.40 ml (2.89 mmol) of triethylamine and 0.19 ml (2.41 mmol) ofmethanesulfonyl chloride to give compound (ab-47) (572 mg; 94% yield).

(Step 3) Synthesis of Compound (Ib-12)

According to the method of Example 2 Step 2, 547 mg (0.87 mmol) ofcompound (Ib-47) was treated with 242 mg (4.34 mmol) of iron powder and232 mg (4.34 mmol) of ammonium chloride to give compound (Ib-12) (461mg;89 % yield).

(Step 4) Synthesis of Compound (Ib-21)

To a solution of 110 mg (0.18 mmol) of compound (Ib-12) in 1.8 ml ofdichloromethane was added 0.03 ml (0.22 mmol) of trifluoroaceticanhydride under ice-cooling and the mixture was stirred for 2 hours atroom temperature. The solution was diluted with ethyl acetate, washedwith water, 5% aqueous solution of sodium hydrogencarbonate andsaturated brine successively, dried and concentrated. The residue wascrystallized from diethylether-hexane to give compound (Ib-21) (122 mg;96% yield).

(Step 5) Synthesis of Compound (Ib-11)

A mixture of 122 mg (0.18 mmol) of compound (Ib-21), 24 mg of 20%palladium hydroxide-carbon in 1.8 ml of methanol and 1.8 ml of1,4-dioxane was stirred for 15 hours under a nitrogen atmosphere at roomtemperature. After an insoluble material was filtered off with celite,the filtrate was concentrated to give 110 mg of the residue.

To a solution of the residue in 3.5 ml of N,N-dimethylformamide wereadded 73 mg (0.53 mmol) of potassium carbonate and 0.05 ml (0.39 mmol)of prenyl bromide successively and the mixture was stirred for 4 hours.The solution was diluted with ethyl acetate, washed with water andsaturated brine successively, dried and concentrated. The residue waspurified by silica gel chromatography (hexane-ethyl acetate 7:3) andcrystallized from diethyl ether-hexane to give compound (Ib-11) (121 mg,93% yield).

(Step 6) Synthesis of Compound (Ib-16)

According to the method of Example 1 Step 7, compound (Ib-16) wasobtained (73 mg; 99% yield) from 111 mg (0.15 mmol) of compound (Ib-11).

Example 4 Synthesis of Compounds (Ic-23) and (Ic-24)

 

(Step 1) Synthesis of Compound (9)

According to the method of Example 1 Step 1, 500 mg (2.35 mmol) ofcompound (8) was reacted with 883 mg (2.46 mmol) of boronic acid (1) togive compound (9) (983 mg; 94% yield).

(Step 2) Synthesis of Compound (10)

To a solution of 983 mg (2.20 mmol) of compound (9) in 10 ml oftetrahydrofuran was added 1 M tetrabutylammonium fluoride in 2.2 ml(2.20 mmol) of tetrahydrofuran under ice-cooling and the mixture wasstirred for an hour at room temperature. The solution was poured intowater, extracted with ethyl acetate. washed with saturated brine driedand concentrated. The residue was dissolved in 10 ml of tetrahydrofuran,then 0.46 ml (3.29 mmol) of triethylamine and 0.20 ml (2.64 mmol) ofmethanesulfonyl chloride was successively added to the solution underice-cooling and the mixture was stirred for 30 minutes at the sametemperature. The solution was diluted with ethyl acetate, washed withwater, 5% aqueous solution of sodium hydrogencarbonate, saturated brinesuccessively, dried and concentrated. The residue was purified by silicagel chromatography (hexane-ethyl acetate 7:3) to give compound (10) (881mg; 98% yield).

(Step 3) Synthesis of Compound (11)

A solution of 120 mg (0.29 mmol) of compound (10) and 11 mg of 10%palladium-carbon in 2 ml of methanol and 2 ml of 1,4-dioxane was stirredunder a nitrogen atmosphere at room temperature for 2 hours. Aninsoluble material was filtered off with celite and the filtrate wasconcentrated. To a solution of the residue in 3 ml of methanol was added11 mg (0.29 mmol) of sodium borohydride under ice-cooling and themixture was stirred for 30 minutes. The solution was poured into waterand extracted with ethyl acetate. The extract was washed with saturatedbrine, dried and concentrated. To a solution of the obtained crudeproduct in 3 ml of acetone were added 122 mg (0.88 mmol) of potassiumcarbonate and 0.10 ml (0.88 mmol) of prenyl bromide successively and themixture was stirred for 2 hours at room temperature. The mixture wasdiluted with ethyl acetate and washed with water and saturated brinesuccessively, dried and concentrated. The residue was purified by silicagel chromatography (hexane-ethyl acetate 7:3) to give compound (11) (108mg; 95% yield).

(Step 4) Synthesis of Compound (Ic-24)

To a solution of 108 mg (0.28 mmol) of compound (11) in 2 ml ofacetonitrile were added 87 mg (0.33 mmol) of triphenylphosphine and 110mg (0.33 mmol) of carbon tetrabromide under ice-cooling and the mixturewas stirred for 1 hour at room temperature. To the mixture were added152 mg (1.38 mmol) of hydroquinone and 114 mg (0.83 mmol) of potassiumcarbonate and the mixture was stirred for 20 hours at room temperature.The mixture was poured into diluted hydrochloric acid and extracted withethyl acetate. The extract was washed with an aqueous solution of 5%sodium hydrogencarbonate and saturated brine, dried and concentrated.The residue was purified by silica gel chromatography (hexane-ethylacetate 7:3) to give compound (Ic-24) (61 mg; 46% yield).

(Step 5) Synthesis of Compound (Ic-23)

According to the method of Example 1 Step 7, compound (Ic-23) wasobtained (34 mg; 69% yield) from 59 mg (0.12 mmol) of compound (Ic-24).

Example 5 Synthesis of Compounds (Ib-539) and (Ib-540)

 

(Step 1) Synthesis of Compound (Ib-539)

The compound (Ib-250) (444 mg, 1 mmol) was dissolved in anhydrous ether(40 mL) under ice-cooling. Chloromethyl chloroformate (194 mg, 1 mmol)and triethylamine (210 ml, 1 mmol) were added successively to thesolution under a nitrogen atmosphere with stirred, and the mixture wasstirred for 4 hours without ice-cooling. Precipitate in the reactionmixture was filtered off and the filtrate was washed with water, driedover sodium sulfuric anhydride and concentrated under reduced pressureto give 540 mg of compound (Ib-539) as oil.

Elementary Analysis for C₃₁H₃₄N₂O₃FCl; Calculated: C, 69.33; H, 6.38; N,5.22; F, 3.54; Cl, 6.60. Analyzed : C, 68.85; H, 6.42; N, 5.21; F, 3.58;Cl, 7.06.

(Step 2) Synthesis of Compound (Ib-540)

A mixture of glycol acid (38 mg, 0.5 mmol), potassium carbonate (35 mg,0.25 mmol) and N,N-dimethylformamide (1 mL) was stirred under reducedpressure at room temperature for 10 minutes. A solution of compound 1(54 mg, 0.1 mmol) in N,N-dimethylformamide (0.5 ml) and potassiumbromide (12 mg, 0.1 mmol) were added and the mixture was vigorouslystirred for 20 hours under an argon atmosphere. The mixture was dilutedwith ether (5 ml) and an insoluble material was filtered off. Thefiltrate was washed with water, dried over sodium sulfate anhydride andconcentrated under reduced pressure. The residual crude product waspurified by silica gel chromatography (elution solvent: hexane-ethylacetate (2:1)) to give 27 mg of compound (Ib-540) as an oil.

Elementary Analysis for C₃₃H₃₇N₂O₆F; Calculated: C, 68.73; H, 6.47; N,4.86; F, 3.29. Analyzed: C, 68.59; H, 6.68; N, 4.98; F, 3.25.

Example 6 Synthesis of Compound (Ib-541)

A mixture of succinic acid (590 mg, 5 mmol), potassium carbonate (345mg, 2.5 mmol) and N,N-dimethylformamide (6 ml) was stirred for 10minutes under reduced pressure at room temperature. The solution ofcompound (Ib-539) (537 mg, 1 mmol) in N,N-dimethylformamide (5 ml)obtained by the method in Example 5 Step 1 and sodium iodide (70 mg, 0.5mmol) were successively added and vigorously stirred for 5 days under anargon atmosphere. The mixture was poured into an aqueous solution of 5%acetic acid and extracted with ether-hexane (4:1). After the obtainedmixture was dried over anhydrous sodium sulfate, the solvent was removedoff. The residual crude product was purified by silica gelchromatography (elution solvent: chloroform-methanol (20:1)) to give 60mg of compound (Ib-541) as an oil.

Elementary Analysis for C₃₅H₃₉N₂O₇F; Calculated: C, 67.95; H, 6.35; N,4.53; F, 3.07. Analyzed: C, 68.25; H, 5.96; N, 4.64; F, 3.13. LSIMS:m/Z=618 [M+H]⁺.

Example 7 Synthesis of Other Compounds (I)

Using analogous procedure, the following compounds (I) were synthesized.The structures and physical constants are shown below. Tables 50 to 55represents partial structures used in Table 56 or later asabbreviations, A1, A2, B1, B2, . . . C1, C2 . . .

TABLE 50

R⁴ R⁵ R⁶ R⁷ X Y A1 H H H H O H A2 H H H H O CH₂-2-furyl A3 H H H H OCH₂C₆H₅ A4 H H H H O CH₂C₆H₄-4-Me A5 H H H H O CH₂CH═CMe₂ A6 OH H H H OCH₂C₆H₅ A7 OAc H H H O CH₂C₆H₅ A8 OMs H H H O CH₂C₆H₅ A9 OSO₂CF₃ H H H OCH₂C₆H₅ A10 OSO₂Ph H H H O CH₂C₆H₅ A11 OMe H H H O CH₂C₆H₅ A12 OH H H HO CH₂C₆H₄-2-Me A13 OH H H H O CH₂C₆H₄-3-Me A14 OH H H H O CH₂C₆H₄-4-MeA15 OMs H H H O CH₂C₆H₄-2-Me A16 OMs H H H O CH₂C₆H₄-3-Me A17 OMs H H HO CH₂C₆H₄-4-Me A18 OH H H H O CH₂C₆H₄-2-OMe A19 OH H H H O CH₂C₆H₄-3-OMeA20 OH H H H O CH₂C₆H₄-4-OMe A21 OMs H H H O CH₂C₆H₄-2-OMe A22 OMs H H HO CH₂C₆H₄-3-OMe A23 OMs H H H O CH₂C₆H₄-4-OMe A24 OH H H H O CH₂-2-PyA25 OH H H H O CH₂-3-Py A26 OH H H H O CH₂-4-Py A27 OMs H H H O CH₂-2-PyA28 OMs H H H O CH₂-3-Py A29 OMs H H H O CH₂-4-Py A30 OH H H H OCH₂CH₂C₆H₅ A31 OMs H H H O CH₂CH₂C₆H₅ A32 OH H H H O CH₂CH═CMe₂ A33 OMsH H H O CH₂CH═CMe₂ A34 OH H H H O CH₂CH═CCl₂ A35 OMe H H H O CH₂CH═CMe₂

 

TABLE 51 R⁴ R⁵ R⁶ R⁷ X Y A36 OMe H H H O CH₂CH═CCl₂ A37 F H H H OCH₂CH═CMe₂ A38 F H H H O CH₂CH═CCl₂ A39 OH H H H O CH₂CH₂CH═CMe₂ A40 OMsH H H O CH₂CH₂CH═CMe₂ A41 H H H H NMe Me A42 H H H H NH H A43 H H H H NHMe A44 H H H H NH iPr A45 H H H H NH CH₂CH═CH₂ A46 H H H H NH CH₂CH═CMe₂A47 H H H H NH CH₂C≡CH A48 H H H H NH c-Hex A49 H H H H NH CH₂-c-Hex A50H H H H NH CH₂C₆H₅ A51 H H H H NH CH₂C₆H₄-4-COOMe A52 H H H H NHCH₂C₆H₄-4-COOH A53 H H H H NH CH₂-4-Pyr A54 H H H H NH CH₂-2-furyl A55 HH H H NH CH₂-3-furyl A56 H H H H NH CH₂-2-thienyl A57 H H H H NHCH₂-3-thienyl A58 H H H H NCH₂CH═CMe₂ SO₂NHMe A59 H H H H NMe SO₂NH₂ A60OMe H H H NH CH₂CH═CMe₂ A61 OMe H H H NH CH₂C₆H₅ A62 Me H H H NHCH₂CH═CMe₂ A63 Me H H H NH CH₂C₆H₅ A64 H F H H NH H A65 H F H H NH iPrA66 H F H H NH iBu A67 H F H H NH CH₂CH═CMe₂ A68 H F H H NH cPent A69 HF H H NH cHex A70 H F H H NH CH₂cHex A71 H F H H NH CH₂C₆H₄-4-Et A72 H FH H NH CH₂C₆H₄-4-iPr A73 H F H H NH CH₂C₆H₄-4-COOH A74 H F H H NHCH₂C₆H₄-4-COOMe A75 H F H H N-iPr SO₂NH₂ A76 H F H H N-iPr SO₂NHMe A77 HF H H NCH₂CH═CMe₂ SO₂NHMe

 

TABLE 52 R⁴ R⁵ R⁶ R⁷ X Y A78 F H H H NH CH₂CH═CMe₂ A79 F H H H NHCH₂C₆H₅ A80 H Cl H H NH H A81 H Cl H H NH CH₂CH═CMe₂ A82 H Cl H H NHcHex A83 H Cl H H NH CH₂cHex A84 Cl H H H NH CH₂CH═CMe₂ A85 Cl H H H NHCH₂C₆H₅ A86 H H H H NH 4-tetrahydropyran A87 H H H H NH C₆H₄-4-B(OH)₂A88 H H H H NH CH₂C₆H₄-2-OMe A89 H H H H NH CH₂C₆H₂-3,4,5-(OMe)₃ A90 H HH H NH CH(Me)CH₂OMe A91 H H H H NH CH₂cHex-4,4-(OMe)₂ A92 H H H H NHCH₂C₆H₃-3,4-(OH)₂ A93 H H H H NH CH₂C₆H₄-4-OH A94 H H H H NH

A95 H H H H NH CH₂C₆H₄-3-OH A96 H H H H N-pyrroryl A97 H H H H NHCH₂-2-thienyl A98 H H H H NH cHex-4-(═NOMe) A99 H H H H NH CH₂-2-ThiazolA100 H H H H NH

A101 H H H H NH CH₂C₆H₄-4-OMe A102 H H H H NH

A103 H H H H O CH₂C≡CMe A104 H Me H H NH CH₂CH═CMe₂ A105 H Me H H NHCH₂C₆H₅ A106 H F H H NH CH₂C₆H₅ A107 F H H H O H A108 F H H H O Me A109F H H H O CH₂-2-furyl A110 F H H H O CH₂C₆H₅ A111 H H H H

A112 H H H H S CH₂CH═CMe₂ A113 H H H H SO₂ NH₂ A114 H F H H SO₂ NH₂

 

TABLE 53 R⁴ R⁵ R⁶ R⁷ X Y A115 H H H H NH

A116 H H H H NH CH₂C(Me)═CHMe A117 H H H H NH CH₂C≡CMe A118 H H H HNCH₂CH═CMe₂ CH₂CH═CMe₂ A119 H F H H NCOOCH₂Cl CH₂CH═CMe₂ A120 H F H HNCOOCH₂OCOCH₂OH CH₂CH═CMe₂ A121 H F H H NCOOCH₂OCOCH₂CH₂COOH CH₂CH═CMe₂A122 H F H H NCOOCH₂OCOMe CH₂CH═CMe₂ A123 H F H H NCOOCH(Me)OCOMeCH₂CH═CMe₂ A124 H F H H NCOOCH(Me)OCOCMe₃ CH₂CH═CMe₂ A125 H F H HNCOOCH2OCO(CH₂)₁₄Me CH₂CH═CMe₂ A126 H F H H NCOOCH₂OCO-3-Pyr CH₂CH═CMe₂A127 H F H H NCH₂NHCO—C₆H₄-o- CH₂CH═CMe₂ OCH₂OCOMe A128 H H H HNCOOCH₂OCOCH₂OH CH₂CH═CMe₂ A129 H H H H NCOOCH₂OCOMe CH₂CH═CMe₂ A130 H HH H NCOOCH(Me)OCOCMe₃ CH₂CH═CMe₂ A131 H H H H NCOOCH₂OCO-3-PyrCH₂CH═CMe₂ A132 F H H H NCOOCH₂OCO CH₂CH═CMe₂ CH₂CH₂COOH A133 F H H HNCOOCH(Me)OCOMe CH₂CH═CMe₂ A134 F H H H NCOOCH₂OCO(CH₂)₁₄Me CH₂CH═CMe₂A135 F H H H NCH₂NHCO—C₆H₄-o- CH₂CH═CMe₂ OCH₂OCOMe A136 H F H HNCOOCH₂OCOCH₂OH cPent A137 H F H H NCOOCH₂OCOMe cPent A138 H F H HNCOOCH(Me)OCOCMe₃ cPent A139 H F H H NCOOCH₂OCO-3-Pyr cPent A140 H Cl HH NCOOCH₂OCO CH₂CH═CMe₂ CH₂CH₂COOH A141 H Cl H H NCOOCH(Me)OCOMeCH₂CH═CMe₂ A142 H Cl H H NCOOCH2OCO(CH₂)₁₄Me CH₂CH═CMe₂ A143 H Cl H HNCH₂NHCO—C₆H₄-o- CH₂CH═CMe₂ OCH₂OCOMe

 

TABLE 54

R⁸ R⁹ R¹⁰ R¹¹ B1 OMe H H OMe B2 OMe H OH OMe B3 OMe H OMs OMe B4 Me H HMe B5 Me H OH Me B6 Me H OMs Me B7 Me Me Me Me B8 Me Me OMe Me B9 Me MeOH Me B10 Me Me Me OMe B11 Me Me Me OH B12 OMe Me Me OMe B13 Me H Me MeB14 Me Me H Me B15 Me H F Me B16 Me F H Me B17 OMe H H Me B18 Me H H OMeB19 Cl H H Cl B20 OEt H H OEt B21 OiPr H H OiPr B22 OcPr H H OcPr B23OMe Me Me COOMe B24 Me Me Me COOMe B25 SMe H H SMe B26 SEt H H SEt B27COOMe Me Me OMe B28 Me Me Me Cl B29 Me OMe H Me B30 COOMe Me Me Me B31Cl Me Me Me B32 H Me Me Cl B33 Me H Cl Me B34 H Me Cl H B35 Me H H ClB36 Me Me H H B37 H Me H Me B38 Me H Me H B39 OMe OMe H H B40 H OMe HOMe B41 OMe H OMe H B42 H Me H OMe B43 OMe H Me H

 

TABLE 55

R¹² R¹³ R¹⁴ R¹⁵ —X′—Y′ C1 H H H H H C2 H H H H OH C3 H H H H OMs C4 H HH H OMe C5 H H H H NH₂ C6 H H H H NMe₂ C7 H H H H SMe C8 H H H H Ms C9 HH H H F C10 H CF₃ H H H C11 H NO₂ H H H C12 H NH₂ H H H C13 H NHAc H H HC14 H NHMs H H H C15 H N(Ms)CH₂CH═CMe₂ H H H C16 H OH H H OCH₂C₆H₅ C17 HOMs H H OCH₂C₆H₅ C18 H OH H H OCH₂CH═CMe₂ C19 H OMe H H OCH₂CH═CMe₂ C20H OMs H H OCH₂CH═CMe₂ C21 NO₂ H H H H C22 NH₂ H H H H C23 NHAc H H H HC24 NHMs H H H H C25 Cl H H H NO₂ C26 Cl H H H NH₂ C27 Cl H H H NHMs C28Cl H H H NHCOCF₃ C29 Cl H H H NHCH₂CH═CMe₂ C30 H H H H NHCH₂CH═CMe₂

 

TABLE 56

      No.

      R⁸       R⁹       R¹⁰       R¹¹       A       C Ia-1 S1 H H H — A6C2 Ia-2 S1 H H H — A32 C2 Ia-3 S1 H H H — A35 C2 Ia-4 S1 H H H — A6 C3Ia-5 S1 H H H — A8 C3 Ia-6 S1 H H H — A33 C3 Ia-7 S1 H H H — A35 C3 Ia-8S1 H H H — A6 C4 Ia-9 S1 H H H — A8 C4 Ia-10 S1 H H H — A32 C4 Ia-11 S1H H H — A33 C4 Ia-12 S1 H H H — A8 C17 Ia-13 S1 H H H — A32 C18 Ia-14 S1H H H — A33 C19 Ia-15 S1 H H Cl — A6 C2 Ia-16 S1 H H Cl — A32 C2 Ia-17S1 H H Cl — A8 C3 Ia-18 S1 H H Cl — A33 C3 Ia-19 S1 H H Cl — A35 C6Ia-20 S1 Me H H — A6 C2 Ia-21 S1 Me H H — A32 C2 Ia-22 S1 Me H H — A35C2 Ia-23 S1 Me H H — A6 C3 Ia-24 S1 Me H H — A8 C3 Ia-25 S1 Me H H — A33C3 Ia-26 S1 Me H H — A35 C3 Ia-27 S1 H Me H — A6 C2

 

TABLE 57 No.

R⁸ R⁹ R¹⁰ R¹¹ A C Ia-28 S1 H Me H — A32 C2 Ia-29 S1 H Me H — A35 C2Ia-30 S1 H Me H — A6 C3 Ia-31 S1 H Me H — A8 C3 Ia-32 S1 H Me H — A33 C3Ia-33 S1 H Me H — A35 C3 Ia-34 S1 H H Me — A6 C2 Ia-35 S1 H H Me — A32C2 Ia-36 S1 H H Me — A35 C2 Ia-37 S1 H H Me — A6 C3 Ia-38 S1 H H Me — A8C3 Ia-39 S1 H H Me — A33 C3 Ia-40 S1 H H Me — A35 C3 Ia-41 S1 H Me Me —A6 C2 Ia-42 S1 H Me Me — A32 C2 Ia-43 S1 H Me Me — A35 C2 Ia-44 S1 H MeMe — A37 C2 Ia-45 S1 H Me Me — A6 C3 Ia-46 S1 H Me Me — A8 C3 Ia-47 S1 HMe Me — A33 C3 Ia-48 S1 H Me Me — A35 C3 Ia-49 S1 H Me Me — A6 C6 Ia-50S1 H Me Me — A32 C6 Ia-51 S1 H Me Me — A34 C6 Ia-52 S1 H Me Me — A35 C6Ia-53 S1 H Me Me — A36 C6 Ia-54 S1 H Me Me — A37 C6 Ia-55 S1 H Me Me —A38 C6 Ia-56 S1 Me Me Me — A6 C2 Ia-57 S1 Me Me Me — A32 C2 Ia-58 S1 MeMe Me — A35 C2 Ia-59 S1 Me Me Me — A37 C2 Ia-60 S1 Me Me Me — A6 C3Ia-61 S1 Me Me Me — A8 C3 Ia-62 S1 Me Me Me — A33 C3 Ia-63 S1 Me Me Me —A35 C3 Ia-64 S2 H H — H A6 C2

 

TABLE 58 No.

R⁸ R⁹ R¹⁰ R¹¹ A C Ia-65 S2 H H — H A8 C2 Ia-66 S2 H H — H A32 C2 Ia-67S2 H H — H A35 C2 Ia-68 S2 H H — H A8 C3 Ia-69 S2 H H — H A33 C3 Ia-70S2 H H — H A35 C3 Ia-71 S2 Me H — H A6 C2 Ia-72 S2 Me H — H A8 C2 Ia-73S2 Me H — H A32 C2 Ia-74 S2 Me H — H A35 C2 Ia-75 S2 Me H — H A8 C3Ia-76 S2 Me H — H A33 C3 Ia-77 S2 Me H — H A35 C3 Ia-78 S2 H Me — H A6C2 Ia-79 S2 H Me — H A8 C2 Ia-80 S2 H Me — H A32 C2 Ia-81 S2 H Me — HA35 C2 Ia-82 S2 H Me — H A8 C3 Ia-83 S2 H Me — H A33 C3 Ia-84 S2 H Me —H A35 C3 Ia-85 S2 H H — Me A6 C2 Ia-86 S2 H H — Me A8 C2 Ia-87 S2 H H —Me A32 C2 Ia-88 S2 H H — Me A35 C2 Ia-89 S2 H H — Me A8 C3 Ia-90 S2 H H— Me A33 C3 Ia-91 S2 H H — Me A35 C3 Ia-92 S2 Me H — Me A6 C2 Ia-93 S2Me H — Me A8 C2 Ia-94 S2 Me H — Me A32 C2 Ia-95 S2 Me H — Me A35 C2Ia-96 S2 Me H — Me A8 C3 Ia-97 S2 Me H — Me A33 C3 Ia-98 S2 Me H — MeA35 C3 Ia-99 S2 Me H — Me A6 C6 Ia-100 S2 Me H — Me A32 C6 Ia-101 S2 MeH — Me A34 C6

 

TABLE 59 No.

R⁸ R⁹ R¹⁰ R¹¹ A C Ia-102 S2 Me H — Me A35 C6 Ia-103 S2 Me H — Me A36 C6Ia-104 S2 Me H — Me A37 C6 Ia-105 S2 Me H — Me A38 C6 Ia-106 S2 Me Me —Me A6 C2 Ia-107 S2 Me Me — Me A8 C2 Ia-108 S2 Me Me — Me A32 C2 Ia-109S2 Me Me — Me A35 C2 Ia-110 S2 Me Me — Me A8 C3 Ia-111 S2 Me Me — Me A33C3 Ia-112 S2 Me Me — Me A35 C3 Ia-113 S2 Me Me — Me A6 C6 Ia-114 S2 MeMe — Me A32 C6 Ia-115 S2 Me Me — Me A34 C6 Ia-116 S2 Me Me — Me A35 C6Ia-117 S2 Me Me — Me A37 C6 Ia-118 S3 Me — H — A6 C2 Ia-119 S3 Me — H —A32 C2 Ia-120 S3 Me — H — A35 C2 Ia-120 S3 OMe — H — A6 C2 Ia-121 S3 OMe— H — A32 C2 Ia-122 S3 OMe — H — A35 C2 Ia-123 S3 Me — Me — A6 C2 Ia-124S3 Me — Me — A32 C2 Ia-125 S3 Me — OMe — A11 C1 Ia-126 S3 Me — Me — A35C2 Ia-127 S3 Me — OMe — A3 C1 Ia-128 S3 Me — OMe — A4 C1 Ia-129 S3 Me —OMe — A5 C1 Ia-131 S3 Me — OMe — A6 C1 Ia-132 S3 Me — OMe — A7 C1 Ia-133S3 Me — OMe — A8 C1 Ia-134 S3 Me — OMe — A9 C1 Ia-135 S3 Me — OMe — A10C1 Ia-136 S3 Me — OMe — A12 C1 Ia-137 S3 Me — OMe — A13 C1 Ia-138 S3 Me— OMe — A14 C1 Ia-139 S3 Me — OMe — A15 C1

 

TABLE 60 No.

R⁸ R⁹ R¹⁰ R¹¹ A C Ia-140 S3 Me — OMe — A16 C1 Ia-141 S3 Me — OMe — A17C1 Ia-142 S3 Me — OMe — A18 C1 Ia-143 S3 Me — OMe — A19 C1 Ia-144 S3 Me— OMe — A20 C1 Ia-145 S3 Me — OMe — A21 C1 Ia-146 S3 Me — OMe — A22 C1Ia-147 S3 Me — OMe — A23 C1 Ia-148 S3 Me — OMe — A24 C1 Ia-149 S3 Me —OMe — A25 C1 Ia-150 S3 Me — OMe — A26 C1 Ia-151 S3 Me — OMe — A27 C1Ia-152 S3 Me — OMe — A28 C1 Ia-153 S3 Me — OMe — A29 C1 Ia-154 S3 Me —OMe — A30 C1 Ia-155 S3 Me — OMe — A31 C1 Ia-156 S3 Me — OMe — A32 C1Ia-157 S3 Me — OMe — A33 C1 Ia-158 S3 Me — OMe — A35 C1 Ia-159 S3 Me —OMe — A39 C1 Ia-160 S3 Me — OMe — A40 C1 Ia-161 S3 Me — OMe — A6 C2Ia-162 S3 Me — OMe — A8 C2 Ia-163 S3 Me — OMe — A32 C2 Ia-164 S3 Me —OMe — A33 C2 Ia-165 S3 Me — OMe — A35 C2 Ia-166 S3 Me — OMe — A37 C2Ia-167 S3 Me — OMe — A8 C3 Ia-168 S3 Me — OMe — A33 C3 Ia-169 S3 Me —OMe — A32 C4 Ia-170 S3 Me — OMe — A35 C4 Ia-171 S3 Me — OMe — A32 C6Ia-172 S3 Me — OMe — A35 C6 Ia-173 S3 Me — OMe — A8 C7 Ia-174 S3 Me —OMe — A32 C7 Ia-175 S3 Me — OMe — A8 C8 Ia-176 S3 Me — OMe — A8 C9Ia-177 S3 Me — OMe — A32 C9 Ia-178 S3 Me — OMe — A33 C9

 

TABLE 61 No.

R⁸ R⁹ R¹⁰ R¹¹ A C Ia-179 S3 Me — OMe — A8 C10 Ia-180 S3 Me — OMe — A32C10 Ia-181 S3 Me — OMe — A33 C10 Ia-182 S3 Me — OMe — A6 C11 Ia-183 S3Me — OMe — A8 C11 Ia-184 S3 Me — OMe — A8 C12 Ia-185 S3 Me — OMe — A8C13 Ia-186 S3 Me — OMe — A8 C14 Ia-187 S3 Me — OMe — A32 C14 Ia-188 S3Me — OMe — A8 C15 Ia-189 S3 Me — OMe — A32 C15 Ia-190 S3 Me — OMe — A33C15 Ia-191 S3 Me — OMe — A6 C21 Ia-192 S3 Me — OMe — A8 C21 Ia-193 S3 Me— OMe — A6 C22 Ia-194 S3 Me — OMe — A8 C23 Ia-195 S3 Me — OMe — A32 C23Ia-196 S3 Me — OMe — A33 C23 Ia-197 S3 Me — OMe — A8 C24 Ia-198 S3 Me —OEt — A6 C1 Ia-199 S3 Me — OEt — A8 C1 Ia-200 S3 Me — OEt — A14 C1Ia-201 S3 Me — OEt — A17 C1 Ia-202 S3 Me — OEt — A32 C1 Ia-203 S3 Me —OEt — A33 C1 Ia-204 S3 Me — OEt — A6 C2 Ia-205 S3 Me — OEt — A32 C2Ia-206 S3 Me — O^(i)Pr — A6 C1 Ia-207 S3 Me — O^(i)Pr — A8 C1 Ia-208 S3Me — O^(i)Pr — A14 C1 Ia-209 S3 Me — O^(i)Pr — A17 C1 Ia-210 S3 Me —O^(i)Pr — A32 C1 Ia-211 S3 Me — O^(i)Pr — A33 C1 Ia-212 S3 Me — O^(i)Pr— A6 C2 Ia-213 S3 Me — O^(i)Pr — A32 C2 Ia-214 S3 Et — OMe — A6 C1Ia-215 S3 Et — OMe — A8 C1 Ia-216 S3 Et — OMe — A14 C1 Ia-217 S3 Et —OMe — A17 C1

 

TABLE 62 No.

R⁸ R⁹ R¹⁰ R¹¹ A C Ia-218 S3 Et — OMe — A32 C1 Ia-219 S3 Et — OMe — A33C1 Ia-220 S3 Et — OMe — A6 C2 Ia-221 S3 Et — OMe — A32 C2 Ia-222 S3 H —CO₂H — A6 C1 Ia-223 S3 H — CO₂H — A8 C1 Ia-224 S3 H — CO₂H — A32 C1Ia-225 S3 H — CO₂H — A33 C1 Ia-226 S3 H — CO₂Me — A6 C1 Ia-227 S3 H —CO₂Me — A8 C1 Ia-228 S3 H — CO₂Me — A11 C1 Ia-229 S3 H — CO₂Me — A32 C1Ia-230 S3 H — CO₂Me — A33 C1 Ia-231 S3 H — CH₂OH — A32 C1 Ia-232 S3 H —CH₂OAc — A8 C1 Ia-233 S3 Me — SMe — A8 C1 Ia-234 S3 Me — SMe — A32 C1Ia-235 S3 Me — NHMe — A6 C1 Ia-236 S3 Me — NHMe — A8 C1 Ia-237 S3 Me —NHMe — A32 C1 Ia-238 S4 — Me — OMe A32 C2 Ia-239 S4 — Me — OMe A6 C3Ia-240 S4 — Me — OMe A8 C3 Ia-241 S4 — Me — OMe A33 C3 Ia-242 S4 — Me —OMe A35 C6 Ia-243 S4 — Me — Me A32 C2 Ia-244 S4 — Me — Me A6 C3 Ia-245S4 — Me — Me A8 C3 Ia-246 S4 — Me — Me A33 C3 Ia-247 S4 — Me — Me A35 C6Ia-248 S5 H H — — A6 C1 Ia-249 S5 H H — — A8 C1 Ia-250 S5 H H — — A32 C1Ia-251 S5 H H — — A33 C1 Ia-252 S5 H H — — A32 C2 Ia-253 S5 H H — — A8C3 Ia-254 S5 H H — — A33 C3 Ia-255 S5 H H — — A6 C4 Ia-256 S5 H H — — A8C4 Ia-257 S5 H H — — A32 C4

 

TABLE 63 No.

R⁸ R⁹ R¹⁰ R¹¹ A C Ia-258 S5 H H — — A33 C4 Ia-259 S5 H H — — A35 C6Ia-260 S5 Me Me — — A32 C2 Ia-261 S5 Me Me — — A35 C2 Ia-262 S5 Me Me —— A35 C6 Ia-263 S6 H — — H A32 C2 Ia-264 S6 H — — H A35 C2 Ia-265 S6 H —— H A35 C6 Ia-266 S6 Me — — Me A32 C2 Ia-267 S6 Me — — Me A35 C2 Ia-268S6 Me — — Me A35 C6 Ia-269 S7 H H — — A6 C2 Ia-270 S7 H H — — A8 C2Ia-271 S7 H H — — A32 C2 Ia-272 S7 H H — — A8 C3 Ia-273 S7 H H — — A33C3 Ia-274 S7 H H — — A35 C6 Ia-275 S7 H H — — A6 C16 Ia-276 S7 Me H — —A8 C2 Ia-277 S7 Me H — — A32 C2 Ia-278 S7 Me H — — A8 C3 Ia-279 S7 Me H— — A33 C3 Ia-280 S7 H Me — — A8 C2 Ia-281 S7 H Me — — A32 C2 Ia-282 S7H Me — — A8 C3 Ia-283 S7 H Me — — A33 C3 Ia-284 S7 Me Me — — A8 C2Ia-285 S7 Me Me — — A32 C2 Ia-286 S7 Me Me — — A8 C3 Ia-287 S7 Me Me — —A33 C3 Ia-288 S7 Me Me — — A35 C6 Ia-289 S8 H H — — A32 C2 Ia-290 S8 H H— — A35 C2 Ia-291 S8 H H — — A35 C6 Ia-292 S8 Me H — — A32 C2 Ia-293 S8Me H — — A35 C2 Ia-294 S8 Me H — — A35 C6 Ia-295 S8 H Me — — A32 C2Ia-296 S8 H Me — — A35 C2 Ia-297 S8 H Me — — A35 C6

 

TABLE 64 No.

R⁸ R⁹ R¹⁰ R¹¹ A C Ia-298 S8 Me Me — — A32 C2 Ia-299 S8 Me Me — — A35 C2Ia-300 S8 Me Me — — A35 C6 Ia-301 S9 Me Me — — A6 C1 Ia-302 S9 Me Me — —A8 C1 Ia-303 S9 Me Me — — A32 C1 Ia-304 S9 Me Me — — A33 C1 Ia-305 S9 MeMe — — A6 C4 Ia-306 S9 Me Me — — A8 C4 Ia-307 S9 Me Me — — A32 C4 Ia-308S9 Me Me — — A33 C4 Ia-309 S9 Me OMe — — A6 C1 Ia-310 S9 Me OMe — — A8C1 Ia-311 S9 Me OMe — — A14 C1 Ia-312 S9 Me OMe — — A17 C1 Ia-313 S9 MeOMe — — A32 C1 Ia-314 S9 Me OMe — — A33 C1 Ia-315 S9 Me OMe — — A6 C4Ia-316 S9 Me OMe — — A8 C4 Ia-317 S9 Me OMe — — A14 C4 Ia-318 S9 Me OMe— — A17 C4 Ia-319 S9 Me OMe — — A32 C4 Ia-320 S9 Me OMe — — A33 C4Ia-321 S9 Me OMe — — A35 C4 Ia-322 S9 Me CO₂H — — A33 C4 Ia-323 S9 MeCO₂Et — — A6 C4 Ia-324 S9 Me CO₂Et — — A8 C4 Ia-325 S9 Me CO₂Et — — A32C4 Ia-326 S9 Me CO₂Et — — A33 C4 Ia-327 S9 Me CO₂Et — — A35 C4 Ia-328 S9Me CH₂OH — — A32 C4 Ia-329 S9 Me CH₂OH — — A35 C4 Ia-330 S10 H — — — A6C1 Ia-331 S10 H — — — A8 C1 Ia-332 S10 H — — — A32 C1 Ia-333 S10 H — — —A33 C1 Ia-334 S10 Me — — — A6 C1 Ia-335 S10 Me — — — A8 C1 Ia-336 S10 Me— — — A32 C1

 

TABLE 65 No.

R⁸ R⁹ R¹⁰ R¹¹ A C Ia-337 S10 Me — — — A33 C1 Ia-338 S11 H — — — A6 C1Ia-339 S11 H — — — A8 C1 Ia-340 S11 H — — — A14 C1 Ia-341 S11 H — — —A17 C1 Ia-342 S11 H — — — A32 C1 Ia-343 S11 H — — — A33 C1 Ia-344 S11 Me— — — A6 C1 Ia-345 S11 Me — — — A8 C1 Ia-346 S11 Me — — — A32 C1 Ia-347S11 Me — — — A33 C1 Ia-348 S12 H — — — A6 C1 Ia-349 S12 H — — — A8 C1Ia-350 S12 H — — — A32 C1 Ia-351 S12 H — — — A33 C1 Ia-352 S12 Me — — —A6 C1 Ia-353 S12 Me — — — A8 C1 Ia-354 S12 Me — — — A32 C1 Ia-355 S12 Me— — — A33 C1 Ia-356 S2 Me H — Me A37 C30 Ia-357 S1 H Me Me — A37 C30

 

TABLE 66

      No.

      R¹²       R¹³       R¹⁴       R¹⁵       X′—Y′       B       A Ib-1T1 H H — H H B2 A6 Ib-2 T1 H H — H H B3 A8 Ib-3 T1 H H — H H B2 A32 Ib-4T1 H H — H H B3 A33 Ib-5 T1 H H — H H B2 A35 Ib-6 T1 H H — H H B4 A11Ib-7 T1 H H — H H B4 A32 Ib-8 T1 H H — H H B4 A35 Ib-9 T1 H H — H H B4A1 Ib-10 T1 H H — H H B4 A41 Ib-11 T1 H H — H N(COCF₃)CH₂CH═CMe₂ B3 A33Ib-12 T1 H H — H NH₂ B3 A8 Ib-13 T1 H H — H NH₂ B4 A35 Ib-14 T1 H H — HNH₂ B4 A1 Ib-15 T1 H H — H NH₂ B4 A41 Ib-16 T1 H H — H NHCH₂CH═CMe₂ B2A32 Ib-17 T1 H H — H NHCH₂CH═CMe₂ B4 A35 Ib-18 T1 H H — H NHCH₂CH═CMe₂B1 A41 Ib-19 T1 H H — H NHCH₂CH═CMe₂ B4 A1 Ib-20 T1 H H — H NHCH₂CH═CMe₂B4 A41

 

TABLE 67 No.

R¹² R¹³ R¹⁴ R¹⁵ X′—Y′ B A Ib-21 T1 H H — H NHCOCF₃ B3 A8 Ib-22 T1 H H —H NHCOCF₃ B3 A33 Ib-23 T1 H H — H NHCOCF₃ B4 A35 Ib-24 T1 H H — HNHCOCF₃ B4 A1 Ib-25 T1 H H — H NHCOCF₃ B4 A41 Ib-26 T1 H H — H NHCOMe B2A32 Ib-27 T1 H H — H NHCOMe B3 A33 Ib-28 T1 H H — H NHCOMe B4 A35 Ib-29T1 H H — H NHCOMe B4 A1 Ib-30 T1 H H — H NHCOMe B4 A41 Ib-31 T1 H H — HNHSO₂Et B1 A41 Ib-32 T1 H H — H NHSO₂Et B4 A1 Ib-33 T1 H H — H NHSO₂EtB4 A41 Ib-34 T1 H H — H NHMs B2 A32 Ib-35 T1 H H — H NHMs B1 A41 Ib-36T1 H H — H NHMs B4 A1 Ib-37 T1 H H — H NHMs B4 A41 Ib-38 T1 H H — H NMe₂B2 A6 Ib-39 T1 H H — H NMe₂ B3 A8 Ib-40 T1 H H — H NMe₂ B2 A32 Ib-41 T1H H — H NMe₂ B3 A33 Ib-42 T1 H H — H NMe₂ B2 A35 Ib-43 T1 H H — H NMe₂B4 A32 Ib-44 T1 H H — H NMe₂ B4 A35 Ib-45 T1 H H — H NMe₂ B5 A32 Ib-46T1 H H — H NO₂ B2 A6 Ib-47 T1 H H — H NO₂ B3 A8 Ib-48 T1 H H — H NO₂ B4A1 Ib-49 T1 H H — H NO₂ B4 A41 Ib-50 T2 H H H — Cl B4 A1 Ib-51 T2 H H H— Cl B4 A41 Ib-52 T2 H H H — H B2 A6 Ib-53 T2 H H H — H B3 A8 Ib-54 T2 HH H — H B2 A32 Ib-55 T2 H H H — H B3 A33 Ib-56 T2 H H H — H B2 A35 Ib-57T2 H H H — H B4 A32 Ib-58 T2 H H H — H B4 A35 Ib-59 T2 H H H — H B4 A1Ib-60 T2 H H H — H B4 A41

 

TABLE 68 No.

R¹² R¹³ R¹⁴ R¹⁵ X′—Y′ B A Ib-61 T2 H H H — NH₂ B2 A6 Ib-62 T2 H H H —NH₂ B3 A8 Ib-63 T2 H H H — NH₂ B1 A41 Ib-64 T2 H H H — NH₂ B4 A1 Ib-65T2 H H H — NH₂ B4 A41 Ib-66 T2 H H Me — NH₂ B4 A1 Ib-67 T2 H H Me — NH₂B4 A41 Ib-68 T2 H H H — NHCH₂CH═CMe₂ B4 A1 Ib-69 T2 H H H — NHCH₂CH═CMe₂B4 A41 Ib-70 T2 H H Me — NHCH₂CH═CMe₂ B4 A1 Ib-71 T2 H H Me —NHCH₂CH═CMe₂ B4 A41 Ib-72 T2 H H H — NHCOMe B4 A1 Ib-73 T2 H H H —NHCOMe B4 A41 Ib-74 T2 H H Me — NHCOMe B4 A1 Ib-75 T2 H H Me — NHCOMe B4A41 Ib-76 T2 H H H — NHMs B4 A1 Ib-77 T2 H H H — NHMs B4 A41 Ib-78 T2 HH Me — NHMs B4 A1 Ib-79 T2 H H Me — NHMs B4 A41 Ib-80 T2 H H H — NMe₂ B2A6 Ib-81 T2 H H H — NMe₂ B3 A8 Ib-82 T2 H H H — NMe₂ B2 A32 Ib-83 T2 H HH — NMe₂ B3 A33 Ib-84 T2 H H H — NMe₂ B4 A32 Ib-85 T2 H H H — NMe₂ B4A35 Ib-86 T2 H H H — OCH₂C₆H₅ B4 A1 Ib-87 T2 H H H — OCH₂C₆H₅ B4 A41Ib-88 T2 H H H — OCH₂CH═CMe₂ B1 A41 Ib-89 T2 H H H — OCH₂CH═CMe₂ B4 A1Ib-90 T2 H H H — OCH₂CH═CMe₂ B4 A41 Ib-91 T2 H H H — OMe B2 A6 Ib-92 T2H H H — OMe B3 A8 Ib-93 T2 H H H — OMe B2 A32 Ib-94 T2 H H H — OMe B3A33 Ib-95 T2 H H H — OMe B2 A35 Ib-96 T2 H H H — OMe B4 A32 Ib-97 T2 H HH — OMe B4 A35 Ib-98 T2 H H H — Ms B4 A1 Ib-99 T2 H H H — Ms B4 A41Ib-100 T3 H H H H — B2 A6

 

TABLE 69 No.

R¹² R¹³ R¹⁴ R¹⁵ X′—Y′ B A Ib-101 T3 H H H H — B2 A32 Ib-102 T3 H H H H —B2 A35 Ib-103 T3 H H H H — B3 A8 Ib-104 T3 H H H H — B3 A33 Ib-105 T3 HH H H — B4 A11 Ib-106 T3 H H H H — B4 A32 Ib-107 T3 H H H H — B4 A35Ib-108 T3 H H H H — B4 A37 Ib-109 T3 H H H H — B4 A38 Ib-110 T3 H H H H— B4 A1 Ib-111 T3 H H H H — B4 A41 Ib-112 T4 H H — H — B3 A8 Ib-113 T4 HH — H — B2 A32 Ib-114 T4 H H — H — B3 A33 Ib-115 T4 H H — OMe — B4 A1Ib-116 T4 H H — OMe — B4 A41 Ib-117 T4 H Cl — H — B2 A6 Ib-118 T4 H Cl —H — B3 A8 Ib-119 T4 H Cl — H — B3 A33 Ib-120 T4 H Cl — H — B4 A1 Ib-121T4 H Cl — H — B4 A41 Ib-122 T4 H OH — H — B4 A1 Ib-123 T4 H OH — H — B4A41 Ib-124 T4 H OMe — H — B2 A32 Ib-125 T4 H OMe — H — B4 A35 Ib-126 T4H OMe — H — B4 A1 Ib-127 T4 H OMe — H — B4 A41 Ib-128 T5 H — H — H B2A32 Ib-129 T5 H — H — H B3 A33 Ib-130 T5 H — H — H B4 A35 Ib-131 T5 H —H — OH B4 A35 Ib-132 T5 H — H — OCH₂C₆H₅ B4 A1 Ib-133 T5 H — H —OCH₂C₆H₅ B4 A41 Ib-134 T5 H — H — OCH₂CH═CMe₂ B4 A1 Ib-135 T5 H — H —OCH₂CH═CMe₂ B4 A41 Ib-136 T5 H — H — NMe₂ B2 A32 Ib-137 T5 H — H — NMe₂B4 A35 Ib-138 T5 H — H — NHCH₂CH═CMe₂ B4 A1 Ib-139 T5 H — H —NHCH₂CH═CMe₂ B4 A41 Ib-140 T6 — H — H H B2 A32

 

TABLE 70 No.

R¹² R¹³ R¹⁴ R¹⁵ X′—Y′ B A Ib-141 T6 — H — H H B4 A35 Ib-142 T7 H H — — HB2 A32 Ib-143 T7 H H — — H B3 A33 Ib-144 T7 H H — — Cl B2 A6 Ib-145 T7 HH — — Cl B3 A8 Ib-146 T7 H H — — Cl B2 A32 Ib-147 T7 H H — — Cl B3 A33Ib-148 T7 H H — — Cl B4 A35 Ib-149 T7 H H — — Cl B4 A1 Ib-150 T7 H H — —Cl B4 A41 Ib-151 T7 H H — — NHCH₂CH═CMe₂ B4 A1 Ib-152 T7 H H — —NHCH₂CH═CMe₂ B4 A41 Ib-153 T7 H H — — NMe₂ B2 A6 Ib-154 T7 H H — — NMe₂B3 A8 Ib-155 T7 H H — — NMe₂ B2 A32 Ib-156 T7 H H — — NMe₂ B3 A33 Ib-157T7 H H — — NMe₂ B4 A35 Ib-158 T7 H H — — OCH₂C₆H₅ B4 A1 Ib-159 T7 H H —— OCH₂C₆H₅ B4 A41 Ib-160 T7 H H — — OCH₂CH═CMe₂ B4 A1 Ib-161 T7 H H — —OCH₂CH═CMe₂ B4 A41 Ib-162 T7 H H — — OMe B2 A32 Ib-163 T7 H H — — OMe B4A35 Ib-164 T7 H H — — OMe B4 A1 Ib-165 T7 H H — — OMe B4 A41 Ib-166 T8 H— — H H B2 A6 Ib-167 T8 H — — H H B3 A8 Ib-168 T8 H — — H H B2 A32Ib-169 T8 H — — H H B3 A33 Ib-170 T8 H — — H H B4 A35 Ib-171 T8 H — — HOMe B2 A32 Ib-172 T8 H — — H OMe B4 A35 Ib-173 T8 H — — H NMe₂ B2 A32Ib-174 T8 H — — H NMe₂ B4 A35 Ib-175 T8 H — — H Cl B4 A1 lb-176 T8 H — —H Cl B4 A41 Ib-177 T8 H — — H OCH₂C₆H₅ B4 A1 Ib-178 T8 H — — H OCH₂C₆H₅B4 A41 Ib-179 T8 H — — H OCH₂CH═CMe₂ B4 A1 Ib-180 T8 H — — H OCH₂CH═CMe₂B4 A41

 

TABLE 71 No.

R¹² R¹³ R¹⁴ R¹⁵ X′—Y′ B A Ib-181 T8 H — — H NHCH₂CH═CMe₂ B4 A1 Ib-182 T8H — — H NHCH₂CH═CMe₂ B4 A41 Ib-183 T9 H OCH₂C₆H₅ — — — B4 A1 Ib-184 T9 HOCH₂C₆H₅ — — — B4 A41 Ib-185 T9 H OCH₂CH═CMe₂ — — — B4 A1 Ib-186 T9 HOCH₂CH═CMe₂ — — — B4 A41 Ib-187 T9 H NH₂ — — — B4 A1 Ib-188 T9 H NH₂ — —— B4 A41 Ib-189 T9 H NHCH₂CH═CMe₂ — — — B4 A1 Ib-190 T9 H NHCH₂CH═CMe₂ —— — B4 A41 Ib-191 T9 H NHMs — — — B4 A1 Ib-192 T9 H NHMs — — — B4 A41Ib-193 T10 H OCH₂C₆H₅ — — — B4 A1 Ib-194 T10 H OCH₂C₆H₅ — — — B4 A41Ib-195 T10 H OCH₂CH═CMe₂ — — — B4 A1 Ib-196 T10 H OCH₂CH═CMe₂ — — — B4A41 Ib-197 T10 H NH₂ — — — B4 A1 Ib-198 T10 H NH₂ — — — B4 A41 Ib-199T10 H NHCH₂CH═CMe₂ — — — B4 A1 Ib-200 T10 H NHCH₂CH═CMe₂ — — — B4 A41Ib-201 T10 H NHMs — — — B4 A1 Ib-202 T10 H NHMs — — — B4 A41 Ib-203 T11H H H H — B2 A6 Ib-204 T11 H H H H — B3 A8 Ib-205 T11 H H H H — B2 A32Ib-206 T11 H H H H — B3 A33 Ib-207 T1 H H — H NHCH₂CH═CMe₂ B4 A37 Ib-208T1 H H — H NH₂ B4 A37 Ib-209 T1 H H — H NO₂ B4 A37 Ib-210 T1 H H — H HB4 A5 Ib-211 T1 H H — H H B4 A37 Ib-212 T1 H H — H NH-cHex B4 A37 Ib-213T1 H H — H OMe B4 A37 Ib-214 T1 H H — H OCH₂CH═CMe₂ B4 A37 Ib-215 T1 H H— H NH₂ B7 A37 Ib-216 T1 H H — H NHCH₂CH═CMe₂ B7 A37 Ib-217 T1 H H — HOH B7 A37

 

TABLE 72 No.

R¹² R¹³ R¹⁴ R¹⁵ X′—Y′ B A Ib-218 T2 H H H — OCH₂CH═CMe₂ B1 A64 Ib-219 T2H H H — OCH₂CH═CMe₂ B1 A65 Ib-220 T2 H H H — OCH₂CH═CMe₂ B1 A75 Ib-221T2 H H H — OCH₂CH═CMe₂ B1 A76 Ib-222 T2 H H H — OCH₂CH═CMe₂ B1 A67Ib-223 T2 H H H — OCH₂CH═CMe₂ B1 A77 Ib-224 T2 H H H — OCH₂CH═CMe₂ B4A64 Ib-225 T2 H H H — OCH₂CH═CMe₂ B4 A65 Ib-226 T2 H H H — OCH₂CH═CMe₂B4 A69 Ib-227 T2 H H H — OCH₂CH═CMe₂ B4 A76 Ib-228 T2 H H H —OCH₂CH═CMe₂ B4 A83 Ib-229 T2 H H H — OCH₂CH═CMe₂ B4 A82 Ib-230 T2 H H H— OCH₂CH═CMe₂ B4 A81 Ib-231 T2 H H H — OCH₂CH═CMe₂ B4 A69 Ib-232 T2 H HH — OCH₂CH═CMe₂ B4 A68 Ib-233 T2 H H H — OCH₂CH═CMe₂ B4 A66 Ib-234 T2 HH H — OCH₂CH═CMe₂ B4 A71 Ib-235 T2 H H H — OCH₂CH═CMe₂ B4 A72 Ib-236 T2H H H — OCH₂CH═CMe₂ B4 A73 Ib-237 T2 H H H — OCH₂CH═CMe₂ B4 A74 Ib-238T2 H H H — OCH₂CH═CMe₂ B4 A104 Ib-239 T2 H H H — OCH₂CH═CMe₂ B4 A45Ib-240 T2 H H H — OCH₂CH═CMe₂ B4 A47 Ib-241 T2 H H H — OCH₂CH═CMe₂ B4A49 Ib-242 T2 H H H — OCH₂CH═CMe₂ B4 A48 Ib-243 T2 H H H — OCH₂CH═CMe₂B4 A53 Ib-244 T2 H H H — OCH₂CH═CMe₂ B4 A50 Ib-245 T2 H H H —OCH₂CH═CMe₂ B4 A59 Ib-246 T2 H H H — OCH₂CH═CMe₂ B4 A57 Ib-247 T2 H H H— OCH₂CH═CMe₂ B4 A55 Ib-248 T2 H H H — OCH₂CH═CMe₂ B4 A42 Ib-249 T2 H HH — OCH₂CH═CMe₂ B4 A43 Ib-250 T2 H H H — OCH₂CH═CMe₂ B4 A67 Ib-251 T2 HH H — OCH₂CH═CMe₂ B4 A62 Ib-252 T2 H H H — OCH₂CH═CMe₂ B4 A63

 

TABLE 73 No.

R¹² R¹³ R¹⁴ R¹⁵ X′—Y′ B A Ib-253 T2 H H H — OCH₂CH═CMe₂ B4 A78 Ib-254 T2H H H — OCH₂CH═CMe₂ B4 A79 Ib-255 T2 H H H — OCH₂CH═CMe₂ B4 A84 Ib-256T2 H H H — OCH₂CH═CMe₂ B4 A85 Ib-257 T2 H H H — OCH₂CH═CMe₂ B4 A60Ib-258 T2 H H H — OCH₂CH═CMe₂ B4 A61 Ib-259 T2 H H H — OCH₂CH═CMe₂ B4A46 Ib-260 T2 H NO₂ H — OCH₂CH═CMe₂ B4 A46 Ib-261 T2 H H H — OCH₂CH═CMe₂B4 A107 Ib-262 T2 H H H — OCH₂CH═CMe₂ B4 A37 Ib-263 T2 H H H —OCH₂CH═CMe₂ B4 A108 Ib-264 T2 H H H — OCH₂CH═CMe₂ B4 A109 Ib-265 T2 H HH — OCH₂CH═CMe₂ B4 A110 Ib-266 T2 H H H — OCH₂CH═CMe₂ B4 A113 Ib-267 T2H H H — OCH₂CH═CMe₂ B4 A114 Ib-268 T2 H H Me — OCH₂CH═CMe₂ B4 A67 Ib-269T2 H Me H — OCH₂CH═CMe₂ B4 A67 Ib-270 T2 Me H H — OCH₂CH═CMe₂ B4 A67Ib-271 T2 H Me H — OCH₂CH═CMe₂ B4 A64 Ib-272 T2 Me H H — OCH₂CH═CMe₂ B4A64 Ib-273 T2 H H Me — OCH₂CH═CMe₂ B4 A46 Ib-274 T2 H Me H — OCH₂CH═CMe₂B4 A46 Ib-275 T2 Me H H — OCH₂CH═CMe₂ B4 A46 Ib-276 T2 H H Me —OCH₂CH═CMe₂ B4 A42 Ib-277 T2 H Me H — OCH₂CH═CMe₂ B4 A42 Ib-278 T2 Me HH — OCH₂CH═CMe₂ B4 A42 Ib-279 T2 H H H — OCH₂CH₂F B4 A46 Ib-280 T2 H H H— OCH₂C≡CH B4 A47 Ib-281 T2 H H H — OCH₂CH═CH₂ B4 A45 Ib-282 T2 H H H —CH₂CH₂CH═CMe₂ B4 A67 Ib-283 T2 H H H — NHCH₂CH═CMe₂ B4 A37 Ib-284 T2 H HH — NHCH₂CH═CMe₂ B4 A5 Ib-285 T2 H H H — NH₂ B4 A37 Ib-286 T2 H H H —NH₂ B4 A5 Ib-287 T2 H H H — NH-cHex B4 A5 Ib-288 T2 H H H — OCH₂-2-furylB4 A67

 

TABLE 74 No.

R¹² R¹³ R¹⁴ R¹⁵ X′—Y′ B A Ib-289 T2 H H H — CH2C≡CMe B4 A67 Ib-290 T2 HH H — 1-pyrrolyl B4 A67 Ib-291 T2 H H H — 1-pyrrolidinyl B4 A67 Ib-292T2 H H H — H B4 A5 Ib-293 T2 H H H — OMe B4 A46 Ib-294 T2 H NO₂ H — OMeB4 A46 Ib-295 T2 H H H — OBn B4 A37 Ib-296 T2 H H H — OMe B4 A37 Ib-297T2 H H H — OCH₂CH═CMe₂ B7 A42 Ib-298 T2 H H H — OCH₂CH═CMe₂ B7 A46Ib-299 T2 H H H — OCH₂CH═CMe₂ B7 A44 Ib-300 T2 H H H — OMe B7 A37 Ib-301T2 H H H — NHCH₂CH═CMe₂ B7 A37 Ib-302 T2 H H H — NH-i-Pr B7 A37 Ib-303T2 H H H — NHCH₂-cHex B7 A37 Ib-304 T2 H H H — NHCH₂-3-Pyr B7 A37 Ib-305T2 H H H — NH-i-Pent B7 A37 Ib-306 T2 H H H — NH-i-Bu B7 A37 Ib-307 T2 HH H — NHCH₂-2-thienyl B7 A37 Ib-308 T2 H H H — NHCH₂-3-thienyl B7 A37Ib-309 T2 H H H — NHCH₂-2-furyl B7 A37 Ib-310 T2 H H H — NHCH₂-3-furylB7 A37 Ib-311 T2 H H H — NHCH₂-2-Py B7 A37 Ib-312 T2 H H H — NH₂ B7 A37Ib-313 T2 H H H — NHCH₂CH═CMe₂ B7 A42 Ib-314 T2 H H H — NHCH₂CH═CMe₂ B7A46 Ib-315 T2 H H H — SCH₂CH═CMe₂ B7 A42 Ib-316 T2 H H H — SCH₂CH═CMe₂B7 A46 Ib-317 T2 H H H — SCH₂CH═CMe₂ B7 A111 Ib-318 T2 H H Me —NHCH₂CH═CMe₂ B7 A46 Ib-319 T2 H Me H — NHCH₂CH═CMe₂ B7 A46 Ib-320 T2 MeH H — NHCH₂CH═CMe₂ B7 A46 Ib-321 T2 H H H — NHCH₂CH═CMe₂ B7 A112 Ib-322T2 H H H — NHCH₂CH═CMe₂ B8 A37

 

TABLE 75 No.

R¹² R¹³ R¹⁴ R¹⁵ X′—Y′ B A Ib-323 T2 H H H — OCH₂CH═CMe₂ B8 A42 Ib-324 T2H H H — OCH₂CH═CMe₂ B8 A46 Ib-325 T2 H H H — OCH₂CH═CMe₂ B8 A51 Ib-326T2 H H H — OCH₂CH═CMe₂ B8 A52 Ib-327 T2 H H H — OCH₂CH═CMe₂ B8 A89Ib-328 T2 H H H — OCH₂CH═CMe₂ B8 A54 Ib-329 T2 H H H — OCH₂CH═CMe₂ B10A42 Ib-330 T2 H H H — OCH₂CH═CMe₂ B10 A46 Ib-331 T2 H H H — OCH₂CH═CMe₂B10 A44 Ib-332 T2 H H H — OCH₂CH═CMe₂ B10 A48 Ib-333 T2 H H H —OCH₂CH═CMe₂ B10 A54 Ib-334 T2 H H H — OCH₂CH═CMe₂ B10 A117 Ib-335 T2 H HH — OCH₂CH═CMe₂ B10 A50 Ib-336 T2 H H H — OCH₂CH═CMe₂ B10 A115 Ib-337 T2H H H — OCH₂CH═CMe₂ B10 A116 Ib-338 T2 H H H — OCH₂CH═CMe₂ B10 A89Ib-339 T2 H H H — OCH₂CH═CHMe B10 A46 Ib-340 T2 H H H — OCH₂CH₂CH═CH₂B10 A46 Ib-341 T2 H H H — OCH₂CH═CHEt B10 A46 Ib-342 T2 H H H —OCH₂C≡CMe B10 A46 Ib-343 T2 H H H — OCH₂-2-furyl B10 A46 Ib-344 T2 H H H— OCH₂-2-furyl B10 A42 Ib-345 T2 H H H — OCH₂CH₂F B10 A46 Ib-346 T2 H HH — OCH₂CF₃ B10 A46 Ib-347 T2 H H H — OCH₂-2-furyl B10 A117 Ib-348 T2 HH H — OCH₂C≡CMe B10 A117 Ib-349 T2 H H H — SMe B10 A46 Ib-350 T2 H H H —SO₂Me B10 A46 Ib-351 T2 H H H — OCH₂CH═CMe₂ B12 A42 Ib-352 T2 H H H —OCH₂CH═CMe₂ B12 A46 Ib-353 T2 H H H — OCH₂CH═CMe₂ B12 A58 Ib-354 T2 H HH — OCH₂CH═CMe₂ B12 A48 Ib-355 T2 H H Me — OCH₂CH═CMe₂ B12 A46 Ib-356 T2H Me H — OCH₂CH═CMe₂ B12 A46 Ib-357 T2 Me H H — OCH₂CH═CMe₂ B12 A46

 

TABLE 76 No.

R¹² R¹³ R¹⁴ R¹⁵ X′—Y′ B A Ib-358 T2 H H H — SMe B12 A46 Ib-359 T2 H H H— NHCH₂CH═CMe₂ B12 A46 Ib-360 T2 H H H — NH2 B12 A78 Ib-361 T2 H H H —NHCH₂CH═CMe₂ B12 A78 Ib-362 T2 H H H — NH-cHex B12 A37 Ib-363 T2 H H H —OCH₂CH═CMe₂ B13 A46 Ib-364 T2 H H H — OCH₂CH═CMe₂ B13 A50 Ib-365 T2 H HH — OCH₂CH═CMe₂ B17 A46 Ib-366 T2 H H H — OCH₂CH═CMe₂ B17 A44 Ib-367 T2H H H — OCH₂CH═CMe₂ B17 A50 Ib-368 T2 H H H — OCH₂CH═CMe₂ B17 A94 Ib-369T2 H H H — OCH₂CH═CMe₂ B17 A86 Ib-370 T2 H H H — OCH₂-2-furyl B17 A46Ib-371 T2 H H H — OCH₂-2-furyl B17 A44 Ib-372 T2 H H H — OCH₂-2-furylB17 A94 Ib-373 T2 H H H — OCH₂CH═CMe₂ B23 A46 Ib-374 T2 H H H —OCH₂-2-furyl B23 A46 Ib-375 T2 H H H — OCH₂CH═CMe₂ B28 A46 Ib-376 T2 H HH — OCH₂CH═CMe₂ B28 A50 Ib-377 T2 H H H — OCH₂CH═CMe₂ B29 A104 Ib-378 T2H H H — OCH₂CH═CMe₂ B29 A105 Ib-379 T2 H H H — OCH₂CH═CMe₂ B29 A67Ib-380 T2 H H H — OCH₂CH═CMe₂ B29 A106 Ib-381 T2 H H H — OCH₂CH═CMe₂ B30A46 Ib-382 T2 H H H — OCH₂-2-furyl B30 A46 Ib-383 T2 H H H — OCH₂C≡CMeB30 A46 Ib-384 T4 H Cl — H — B4 A37 Ib-385 T4 H OMe — H — B4 A37 Ib-386T4 H NMe₂ — H — B4 A37 Ib-387 T5 H — H — H B4 A5 Ib-388 T5 H — H — H B4A37 Ib-389 T5 H — H — NH₂ B4 A5 Ib-390 T5 H — H — NH₂ B4 A37 Ib-391 T5 H— H — NHCH₂CH═CMe₂ B4 A5 Ib-392 T5 H — H — NHCH₂CH═CMe₂ B4 A37 Ib-393 T5H — H — NHCH₂CH═CMe₂ B4 A42 Ib-394 T5 H — H — NHCH₂CH═CMe₂ B4 A46

 

TABLE 77 No.

R¹² R¹³ R¹⁴ R¹⁵ X′—Y′ B A Ib-395 T5 H — H — NHCH₂CH═CMe₂ B4 A118 Ib-396T5 H — H — OCH₂CH═CMe₂ B4 A67 Ib-397 T5 H — H — OCH₂CH═CMe₂ B7 A46Ib-398 T5 H — H — NHCH₂CH═CMe₂ B7 A37 Ib-399 T5 H — H — NH₂ B7 A37Ib-400 T5 H — H — NHCH₂CH═CMe₂ B12 A37 Ib-401 T6 — H — H H B4 A5 Ib-402T6 — H — H H B4 A37 Ib-403 T7 H H — — OCH₂CH═CMe₂ B4 A46 Ib-404 T7 H H —— Cl B4 A5 Ib-405 T7 H H — — OMe B4 A5 Ib-406 T7 H H — — NMe₂ B4 A5Ib-407 T7 H H — — Cl B4 A37 Ib-408 T7 H H — — OMe B4 A37 Ib-409 T7 H H —— NMe₂ B4 A37 Ib-410 T7 H H — — NH₂ B4 A5 Ib-411 T7 H H — — NH₂ B4 A37Ib-412 T7 H H — — NHCH₂CH═CMe₂ B4 A5 Ib-413 T7 H H — — NHCH₂CH═CMe₂ B4A37 Ib-414 T7 H H — — NHCH₂CH═CMe₂ B4 A42 Ib-415 T7 H H — — NHCH₂CH═CMe₂B4 A46 Ib-416 T7 H H — — NHCH₂CH═CMe₂ B4 A118 Ib-417 T7 H H — — NH₂ B7A37 Ib-418 T7 H H — — NHCH₂CH═CMe₂ B7 A37 Ib-419 T7 H H — — OCH₂CH═CMe₂B7 A46 Ib-420 T7 H H — — NHCH₂CH═CMe₂ B12 A37 Ib-421 T8 H — — H H B4 A5Ib-422 T8 H — — H H B4 A37 Ib-423 T8 H — — H NH₂ B4 A5 Ib-424 T8 H — — HNH₂ B4 A37 Ib-425 T8 H — — H NH-cHex B4 A5 Ib-426 T8 H — — H NH-cHex B4A37 Ib-427 T8 H — — H NHCH₂CH═CMe₂ B4 A5 Ib-428 T8 H — — H NHCH₂CH═CMe₂B4 A37 Ib-429 T8 H — — H NHCH₂CH═CMe₂ B4 A46 Ib-430 T8 H — — HNHCH₂CH═CMe₂ B4 A118 Ib-431 T8 H — — H OCH₂CH═CMe₂ B7 A46 Ib-432 T8 H —— H NH₂ B7 A37

 

TABLE 78 No.

R¹² R¹³ R¹⁴ R¹⁵ X′—Y′ B A Ib-433 T8 H — — H NHCH₂CH═CMe₂ B7 A37 Ib-434T8 H — — H NHCH₂CH═CMe₂ B7 A42 Ib-435 T8 H — — H NHCH₂CH═CMe₂ B7 A46Ib-436 T8 H — — H NHCH₂CH═CMe₂ B12 A37 Ib-437 T12 H H H — — B4 A64Ib-438 T12 H H H — — B4 A80 Ib-439 T12 H H H — — B4 A81 Ib-440 T12 H H H— — B4 A67 Ib-441 T12 H H H — — B7 A37 Ib-442 T13 H H — — — B7 A37Ib-443 T14 — H H — — B7 A37 Ib-444 T2 H H H — OCH₂CH═CMe₂ B6 A46 Ib-445T2 H H H — OCH₂CH═CMe₂ B11 A46 Ib-446 T2 H H H — OCH₂CH═CMe₂ B14 A46Ib-447 T2 H H H — OCH₂CH═CMe₂ B15 A46 Ib-448 T2 H H H — OCH₂CH═CMe₂ B16A46 Ib-449 T2 H H H — OCH₂CH═CMe₂ B18 A46 Ib-450 T2 H H H — OCH₂CH═CMe₂B19 A46 Ib-451 T2 H H H — OCH₂CH═CMe₂ B20 A46 Ib-452 T2 H H H —OCH₂CH═CMe₂ B21 A46 Ib-453 T2 H H H — OCH₂CH═CMe₂ B22 A46 Ib-454 T2 H HH — OCH₂CH═CMe₂ B23 A46 Ib-455 T2 H H H — OCH₂CH═CMe₂ B24 A46 Ib-456 T2H H H — OCH₂CH═CMe₂ B25 A46 Ib-457 T2 H H H — OCH₂CH═CMe₂ B26 A46 Ib-458T2 H H H — OCH₂CH═CMe₂ B27 A46 Ib-459 T2 H H H — OCH₂CH═CMe₂ B28 A46Ib-460 T2 H H H — OCH₂CH═CMe₂ B29 A46 Ib-461 T2 H H H — OCH₂CH═CMe₂ B30A46 Ib-462 T2 H H H — OCH₂CH═CMe₂ B31 A46 Ib-463 T2 H H H — OCH₂CH═CMe₂B32 A46 Ib-464 T2 H H H — OCH₂CH═CMe₂ B33 A46 Ib-465 T2 H H H —OCH₂CH═CMe₂ B34 A46 Ib-466 T2 H H H — OCH₂CH═CMe₂ B35 A46 Ib-467 T2 H HH — OCH₂CH═CMe₂ B36 A46 Ib-468 T2 H H H — OCH₂CH═CMe₂ B37 A46 Ib-469 T2H H H — OCH₂CH═CMe₂ B38 A46

 

TABLE 79 No.

R¹² R¹³ R¹⁴ R¹⁵ X′—Y′ B A Ib-470 T2 H H H — OCH₂CH═CMe₂ B39 A46 Ib-471T2 H H H — OCH₂CH═CMe₂ B40 A46 Ib-472 T2 H H H — OCH₂CH═CMe₂ B41 A46Ib-473 T2 H H H — OCH₂CH═CMe₂ B42 A46 Ib-474 T2 H H H — OCH₂CH═CMe₂ B43A46 Ib-475 T2 H H H — NHCH₂CH═CMe₂ B4 A2 Ib-476 T2 H H H — NHCH₂CH═CMe₂B4 A3 Ib-477 T2 H H H — NHCH₂CH═CMe₂ B4 A4 Ib-478 T2 H H H —NHCH₂CH═CMe₂ B4 A7 Ib-479 T2 H H H — NHCH₂CH═CMe₂ B4 A9 Ib-480 T2 H H H— NHCH₂CH═CMe₂ B4 A10 Ib-481 T2 H H H — NHCH₂CH═CMe₂ B4 A12 Ib-482 T2 HH H — NHCH₂CH═CMe₂ B4 A13 Ib-483 T2 H H H — NHCH₂CH═CMe₂ B4 A14 Ib-484T2 H H H — NHCH₂CH═CMe₂ B4 A15 Ib-485 T2 H H H — NHCH₂CH═CMe₂ B4 A16Ib-486 T2 H H H — NHCH₂CH═CMe₂ B4 A17 Ib-487 T2 H H H — NHCH₂CH═CMe₂ B4A18 Ib-488 T2 H H H — NHCH₂CH═CMe₂ B4 A19 Ib-489 T2 H H H — NHCH₂CH═CMe₂B4 A20 Ib-490 T2 H H H — NHCH₂CH═CMe₂ B4 A21 Ib-491 T2 H H H —NHCH₂CH═CMe₂ B4 A22 Ib-492 T2 H H H — NHCH₂CH═CMe₂ B4 A23 Ib-493 T2 H HH — NHCH₂CH═CMe₂ B4 A24 Ib-494 T2 H H H — NHCH₂CH═CMe₂ B4 A25 Ib-495 T2H H H — NHCH₂CH═CMe₂ B4 A26 Ib-496 T2 H H H — NHCH₂CH═CMe₂ B4 A27 Ib-497T2 H H H — NHCH₂CH═CMe₂ B4 A28 Ib-498 T2 H H H — NHCH₂CH═CMe₂ B4 A29Ib-499 T2 H H H — NHCH₂CH═CMe₂ B4 A30 Ib-500 T2 H H H — NHCH₂CH═CMe₂ B4A31 Ib-501 T2 H H H — NHCH₂CH═CMe₂ B4 A34 Ib-502 T2 H H H — NHCH₂CH═CMe₂B4 A36 Ib-503 T2 H H H — NHCH₂CH═CMe₂ B4 A39 Ib-504 T2 H H H —NHCH₂CH═CMe₂ B4 A40 Ib-505 T2 H H H — OCH₂CH═CMe₂ B4 A56 Ib-506 T2 H H H— OCH₂CH═CMe₂ B4 A70 Ib-507 T2 H H H — OCH₂CH═CMe₂ B4 A87 Ib-508 T2 H HH — OCH₂CH═CMe₂ B4 A88 Ib-509 T2 H H H — OCH₂CH═CMe₂ B4 A89

 

TABLE 80 No.

R¹² R¹³ R¹⁴ R¹⁵ X′—Y′ B A Ib-510 T2 H H H — OCH₂CH═CMe₂ B4 A90 Ib-511 T2H H H — OCH₂CH═CMe₂ B4 A91 Ib-512 T2 H H H — OCH₂CH═CMe₂ B4 A92 Ib-513T2 H H H — OCH₂CH═CMe₂ B4 A93 Ib-514 T2 H H H — OCH₂CH═CMe₂ B4 A94Ib-515 T2 H H H — OCH₂CH═CMe₂ B4 A95 Ib-516 T2 H H H — OCH₂CH═CMe₂ B4A96 Ib-517 T2 H H H — OCH₂CH═CMe₂ B4 A97 Ib-518 T2 H H H — OCH₂CH═CMe₂B4 A98 Ib-519 T2 H H H — OCH₂CH═CMe₂ B4 A99 Ib-520 T2 H H H —OCH₂CH═CMe₂ B4 A100 Ib-521 T2 H H H — OCH₂CH═CMe₂ B4 A101 Ib-522 T2 H HH — OCH₂CH═CMe₂ B4 A102 Ib-523 T2 H H H — NHCH₂CH═CMe₂ B4 A103 Ib-524 T2H H H — OCH₂CH═CMe₂ B4 A104 Ib-525 T2 H H H — OCH₂CH═CMe₂ B4 A105 Ib-526T2 H H H — OCH₂CH═CMe₂ B4 A106 Ib-527 T2 H H H — NHCH₂CH═CMe₂ B4 A107Ib-528 T2 H H H — NHCH₂CH═CMe₂ B4 A108 Ib-529 T2 H H H — NHCH₂CH═CMe₂ B4A109 Ib-530 T2 H H H — NHCH₂CH═CMe₂ B4 A110 Ib-531 T2 H H H —OCH₂CH═CMe₂ B4 A111 Ib-532 T2 H H H — OCH₂CH═CMe₂ B4 A112 Ib-533 T2 H HH — OCH₂CH═CMe₂ B4 A113 Ib-534 T2 H H H — OCH₂CH═CMe₂ B4 A114 Ib-535 T2H H H — OCH₂CH═CMe₂ B4 A115 Ib-536 T2 H H H — OCH₂CH═CMe₂ B4 A116 Ib-537T2 H H H — OCH₂CH═CMe₂ B4 A117 Ib-538 T2 H H H — OCH₂CH═CMe₂ B4 A118Ib-539 T2 H H H — OCH₂CH═CMe₂ B4 A119 Ib-540 T2 H H H — OCH₂CH═CMe₂ B4A120 Ib-541 T2 H H H — OCH₂CH═CMe₂ B4 A121 Ib-542 T2 H H H — OCH₂CH═CMe₂B4 A122 Ib-543 T2 H H H — OCH₂CH═CMe₂ B4 A123 Ib-544 T2 H H H —OCH₂CH═CMe₂ B4 A124 Ib-545 T2 H H H — OCH₂CH═CMe₂ B4 A125 Ib-546 T2 H HH — OCH₂CH═CMe₂ B4 A126

 

TABLE 81 No.

R¹² R¹³ R¹⁴ R¹⁵ X′—Y′ B A Ib-547 T2 H H H — OCH₂CH═CMe₂ B4 A127 Ib-548T2 H H H — OCH₂CH═CMe₂ B1 A120 Ib-549 T2 H H H — OCH₂CH═CMe₂ B1 A122Ib-550 T2 H H H — OCH₂CH═CMe₂ B1 A124 Ib-551 T2 H H H — OCH₂CH═CMe₂ B1A126 Ib-552 T2 H H H — OCH₂-2-furyl B10 A128 Ib-553 T2 H H H —OCH₂-2-furyl B10 A129 Ib-554 T2 H H H — OCH₂-2-furyl B10 A130 Ib-555 T2H H H — OCH₂-2-furyl B10 A131 Ib-556 T2 H H H —

B12 A132 Ib-557 T2 H H H —

B12 A133 Ib-558 T2 H H H —

B12 A134 Ib-559 T2 H H H —

B12 A135 Ib-560 T5 H — H — OCH₂CH═CMe₂ B4 A121 Ib-561 T5 H — H —OCH₂CH═CMe₂ B4 A123 Ib-562 T5 H — H — OCH₂CH═CMe₂ B4 A125 Ib-563 T5 H —H — OCH₂CH═CMe₂ B4 A127 Ib-564 T2 H H H — OCH₂CH═CMe₂ B4 A136 Ib-565 T2H H H — OCH₂CH═CMe₂ B4 A137 Ib-566 T2 H H H — OCH₂CH═CMe₂ B4 A138 Ib-567T2 H H H — OCH₂CH═CMe₂ B4 A139 Ib-568 T2 H H H — OCH₂CH═CMe₂ B4 A140Ib-569 T2 H H H — OCH₂CH═CMe₂ B4 A141 Ib-570 T2 H H H — OCH₂CH═CMe₂ B4A142 Ib-571 T2 H H H — OCH₂CH═CMe₂ B4 A143 Ib-572 T2 H H H —

B12 A78 Ib-573 T2 H H H —

B12 A78 Ib-574 T2 H H H —

B12 A78 Ib-575 T2 H H H —

B12 A78

 

TABLE 82

No. V² C B A Ic-1 O C2 B4 A32 Ic-2 O C2 B4 A35 Ic-3 O C3 B4 A6 Ic-4 O C3B4 A8 Ic-5 O C3 B4 A11 Ic-6 O C3 B4 A33 Ic-7 O C3 B4 A35 Ic-8 O C5 B4A11 Ic-9 O C5 B4 A35 Ic-10 O C6 B1 A35 Ic-11 O C6 B1 A37 Ic-12 O C6 B4A11 Ic-13 O C6 B4 A32 Ic-14 O C6 B4 A35 Ic-15 O C19 B4 A35 Ic-16 O C25B4 A41 Ic-17 O C26 B4 A41 Ic-18 O C27 B4 A41 Ic-19 O C28 B4 A41 Ic-20 OC29 B4 A41 Ic-21 NH C2 B4 A32 Ic-22 NH C2 B4 A35 Ic-23 OCH₂ C2 B4 A32Ic-24 OCH₂ C2 B4 A33

 

TABLE 83 No. V² C B A Ic-25 OCH₂ C2 B4 A35 Ic-26 OCH₂ C6 B4 A35 Ic-27OCH₂ C19 B4 A35 Ic-28 CH₂O C2 B1 A32 Ic-29 CH₂O C2 B1 A35 Ic-30 CH₂O C2B4 A35 Ic-31 CH₂O C3 B1 A33 Ic-32 CH₂O C3 B4 A33 Ic-33 NHCH₂ C2 B4 A35Ic-34 NHCH₂ C6 B4 A35 Ic-35 CH═CH C2 B4 A32 Ic-36 CH═CH C2 B4 A33 Ic-37CH═CH C2 B4 A35 Ic-38 CH═CH C3 B4 A33 Ic-39 CH═CH C6 B4 A32 Ic-40 CH═CHC6 B4 A35 Ic-41 CH═CH C19 B4 A35 Ic-42 C≡C C2 B4 A32 Ic-43 C≡C C2 B4 A35Ic-44 C≡C C3 B4 A35 Ic-45 C≡C C19 B4 A35 Ic-46 CO C2 B4 A32 Ic-47 CO C2B4 A35 Ic-48 CH(OH) C2 B4 A32 Ic-49 CH(OH) C2 B4 A35

 

TABLE 84

No. V² C

R⁸ R⁹ R¹⁰ A Ie-1 O C6 S1 H H H A6 Ie-2 O C6 S1 H H H A8 Ie-3 O C6 S1 H HH A32 Ie-4 O C9 S1 H H H A6 Ie-5 O C9 S1 H H H A8 Ie-6 O C9 S1 H H H A14Ie-7 O C9 S1 H H H A17 Ie-8 O C9 S1 H H H A32 Ie-9 O C9 S1 H H H A33Ie-10 O C6 S1 H Me Me A32

 

TABLE 85 No. V² C

R⁸ R⁹ R¹⁰ A Ie-11 O C6 S1 H Me Me A35 Ie-12 O C1 S3 Me — OMe A6 Ie-13 OC1 S3 Me — OMe A8 Ie-14 O C1 S3 Me — OMe A14 Ie-15 O C1 S3 Me — OMe A17Ie-16 O C1 S3 Me — OMe A32 Ie-17 O C4 S3 Me — OMe A8 Ie-18 O C4 S3 Me —OMe A14 Ie-19 O C4 S3 Me — OMe A17 Ie-20 O C4 S3 Me — OMe A32 Ie-21 O C4S3 Me — OMe A33 Ie-22 O C9 S3 Me — OMe A6 Ie-23 O C9 S3 Me — OMe A8Ie-24 O C9 S3 Me — OMe A32 Ie-25 O C9 S3 Me — OMe A33 Ie-26 NH C1 S3 Me— OMe A6 Ie-27 NH C1 S3 Me — OMe A8 Ie-28 NH C1 S3 Me — OMe A14 Ie-29 NHC1 S3 Me — OMe A17 Ie-30 NH C1 S3 Me — OMe A32 Ie-31 NH C4 S3 Me — OMeA8 Ie-32 NH C4 S3 Me — OMe A14 Ie-33 NH C4 S3 Me — OMe A17 Ie-34 NH C4S3 Me — OMe A32 Ie-35 NH C4 S3 Me — OMe A33 Ie-36 NH C9 S3 Me — OMe A6Ie-37 NH C9 S3 Me — OMe A8 Ie-38 NH C9 S3 Me — OMe A14 Ie-39 NH C9 S3 Me— OMe A17 Ie-40 NH C9 S3 Me — OMe A32 Ie-41 NH C9 S3 Me — OMe A33

 

TABLE 86

No.

R⁸ R⁹ R¹⁰ A If-1 morpholino S1 H H H A6 If-2 morpholino S1 H H H A8 If-3morpholino S1 H H H A32 If-4 morpholino S1 H H H A33 If-5 morpholino S1H Me Me A6 If-6 morpholino S1 H Me Me A8 If-7 morpholino S1 H Me Me A32If-8 morpholino S1 H Me Me A33 If-9 morpholino S3 Me — OMe A6 If-10morpholino S3 Me — OMe A8 If-11 morpholino S3 Me — OMe A32 If-12morpholino S3 Me — OMe A33 If-13 4-Me-piperazinyl S3 Me — OMe A6 If-144-Me-piperazinyl S3 Me — OMe A8 If-15 4-Me-piperazinyl S3 Me — OMe A32If-16 4-Me-piperazinyl S3 Me — OMe A33 If-17 4-Ph-piperazinyl S3 Me —OMe A6 If-18 4-Ph-piperazinyl S3 Me — OMe A8 If-19 4-Ph-piperazinyl S3Me — OMe A32 If-20 4-Ph-piperazinyl S3 Me — OMe A33 If-21 1-imidazolylS3 Me — OMe A6 If-22 1-imidazolyl S3 Me — OMe A8 If-23 1-imidazolyl S3Me — OMe A32 If-24 1-imidazolyl S3 Me — OMe A33 If-25 1-triazolyl S3 Me— OMe A6 If-26 1-triazolyl S3 Me — OMe A8 If-27 1-triazolyl S3 Me — OMeA32 If-28 1-triazolyl S3 Me — OMe A33 If-29 2-prenyloxypy- S1 H Me MeA46 ridin-5-yl If-30 2-prenyloxypy- S1 H Me Me A42 ridin-5-yl

 

TABLE 87

No.

R⁴ R⁵ R⁶ R⁷ B

R¹² R¹³ R¹⁴ R¹⁵ X—Y X′—Y′ Ig-1 U1 H H — H B7 T2 H H H — OCH₂CH═CMe₂ NH₂Ig-2 U1 H H — H B7 T2 H H H — OCH₂CH═CMe₂ NHCH₂CH═CMe₂ Ig-3 U1 H H — HB12 T2 H H H — OCH₂CH═CMe₂ NH₂ Ig-4 U1 H H — H B12 T2 H H H —OCH₂CH═CMe₂ NHCH₂CH═CMe₂ Ig-5 U1 H H — H B7 T2 H H H — NHCH₂CH═CMe₂NHCH₂CH═CMe₂ Ig-6 U1 H H — H B12 T2 H H H — NHCH₂CH═CMe₂ NHCH₂CH═CMe₂Ig-7 U1 H H — H B12 T5 H — H — OCH₂CH═CMe₂ NH₂ Ig-8 U1 H H — H B12 T5 H— H — OCH₂CH═CMe₂ NHCH₂CH═CMe₂ Ig-9 U1 H H — H B12 T8 H — — HOCH₂CH═CMe₂ NH₂ Ig-10 U1 H H — H B12 T8 H — — H OCH₂CH═CMe₂ NHCH₂CH═CMe₂Ig-11 U2 H H H — B7 T2 H H H — OCH₂CH═CMe₂ NH₂ Ig-12 U2 H H H — B7 T2 HH H — OCH₂CH═CMe₂ NHCH₂CH═CMe₂ Ig-13 U2 H H H — B12 T2 H H H —OCH₂CH═CMe₂ NH₂ Ig-14 U2 H H H — B12 T2 H H H — OCH₂CH═CMe₂ NHCH₂CH═CMe₂Ig-15 U2 H H H — B7 T2 H H H — NHCH₂CH═CMe₂ NHCH₂CH═CMe₂ Ig-16 U2 H H H— B12 T2 H H H — NHCH₂CH═CMe₂ NHCH₂CH═CMe₂ Ig-17 U2 H H H — B12 T5 H — H— OCH₂CH═CMe₂ NH₂ Ig-18 U2 H H H — B12 T5 H — H — OCH₂CH═CMe₂NHCH₂CH═CMe₂ Ig-19 U2 H H H — B12 T8 H — — H OCH₂CH═CMe₂ NH₂ Ig-20 U2 HH H — B12 T8 H — — H OCH₂CH═CMe₂ NHCH₂CH═CMe₂

 

TABLE 88 No. mp, ¹H-NMR Ia-2 195-197° C., ¹H-NMR(CDCl₃-DMSO-d₆)δ1.77(3H,s), 1.82(3H, s), 4.63(2H, J=6.8), 5.52(1H, br t, J=6.8), 6.25(1H, s),6.93-6.98(3H, m), 7.10(1H, dd, J=2.2, 8.3), 7.20(1H, d, J=2.2), 7.69(1H,d, J=8.1), 7.85(1H, dd, J=2.0, 8.1), 7.89(2H, d, J=8.8), 8.53(1H, br s),8.82(1H, d, J=2.0) Ia-4 181-182° C., ¹H-NMR(CDCl₃)δ3.18(3H, s), 5.19(2H,s), 5.78(1H, s), 7.04(1H, d, J=8.3), 7.12(1H, dd, J=2.2, 8.3), 7.25(1H,d, J=2.2), 7.38-7.45(7H, m), 7.76(1H, br d, J=8.3), 7.92(1H, dd, J=2.4,8.3), 8.88(1H, br d, J=2.4) Ia-5 171-172° C., ¹H-NMR(CDCl₃)δ3.40(3H, s),3.43(3H, s), 5.29(2H, s), 7.36-7.53(8H, m), 7.78-7.81(2H, m), 8.09(1H,d, J=8.3), 8.21(1H, dd, J=2.2, 8.3), 8.25(2H, d, J=8.8), 9.02(1H, br s)Ia-6 165-166° C., ¹H-NMR(CDCl₃)δ1.77(3H, s), 1.82(3H, s), 3.18(3H, s),3.25(3H, s), 4.65(2H, d, J=6.8), 5.50(1H, br t, J=6.8), 7.13(1H, d,J=8.5), 7.42(2H, d, J=8.8), 7.53(1H, dd, J=2.2, 8.5), 7.58(1H, d,J=2.2), 7.77(1H, dd, J=0.7, 8.3), 7.92(1H, dd, J=2.2, 8.3), 8.10(2H, d,J=8.8), 8.88(1H, dd, J=0.7, 2.2) Ia-8 176-177° C.,¹H-NMR(CDCl₃)δ3.87(3H, s), 5.18(2H, s), 5.77(1H, s), 7.01(2H, d, J=9.0),7.02(1H, d, J=8.6), 7.11(1H, dd, J=2.2, 8.6), 7.24(1H, d, J=2.2),7.40-7.45(5H, m), 7.71(1H, dd, J=1.0, 8.3), 7.86(1H, dd, J=2.4, 8.3),7.99(2H, d, J=9.0), 8.84(1H, dd, J=1.0, 2.4) Ia-9 187-188° C.,¹H-NMR(CDCl₃)δ3.13(3H, s), 3.88(3H, s), 5.19(2H, s), 7.02(2H, d, J=8.8),7.17(1H, d, J=8.6), 7.37-7.49(5H, m), 7.51(1H, dd, J=2.2, 8.6), 7.59(1H,d, J=2.2), 7.73(1H, br d, J=8.3), 7.86(1H, dd, J=2.4, 8.3), 8.00(2H, d,J=8.8), 8.83(1H, br d, J=2.4) Ia-10 141-142° C., ¹H-NMR(CDCl₃)δ 1.77(3H,s), 1.82(3H, s), 3.88(3H, s), 4.63(2H, d, J=6.8), 5.52(1H, br t, J=6.8),5.79(1H, s), 6.97(1H, d, J=8.3), 7.02(2H, d, J=9.0), 7.11(1H, dd, J=2.2,8.3), 7.21(1H, d, J=2.2), 7.71(1H, dd, J=0.7, 8.3), 7.86(1H, dd, J=2.4,8.3), 7.99(2H, d, J=9.0), 8.85(1H, dd, J=0.7, 2.4) Ia-11 161-162° C.,¹H-NMR(CDCl₃)δ1.77(3H, s), 1.82(3H, s), 3.24(3H, s), 3.88(3H, s),4.65(2H, d, J=6.8), 5.50(1H, br t, J=6.8), 7.02(2H, d, J=9.0), 7.11(1H,d, J=8.5), 7.52(1H, dd, J=2.4, 8.5), 7.57(1H, d, J=2.4), 7.73(1H, dd,J=0.7, 8.3), 7.86(1H, dd, J=2.4, 8.3), 8.00(2H, d, J=9.0), 8.83(1H, dd,J=0.7, 2.4) Ia-12 233-236° C., ¹H-NMR(CDCl₃)δ 3.13(3H, s), 3.14(3H, s),5.20(2H, s), 5.21(2H, s), 7.17(2H, dd, J=1.7, 8.3), 7.36-7.54(11H, m),7.59(1H, d, J=2.4), 7.73(1H, d, J=8.3), 7.78(1H, dd, J=2.4, 8.3),7.98-8.02(2H, m), 8.84(1H, d, J=2.5) Ia-13 150-151° C.,¹H-NMR(CDCl₃)δ1.77(3H, s), 1.82(6H, s), 4.63(4H, d, J=6.8), 5.52(2H, brt, J=6.8), 5.73(1H, s), 5.78(1H, s), 6.97(2H, d, J=8.3), 7.10(1H, dd,J=2.2, 8.3), 7.21(1H, d, J=2.2), 7.57(1H, dd, J=2.2, 8.3), 7.60(1H, d,J=2.2), 7.69(1H, br d, J=8.3), 7.85(1H, dd, J=2.4, 8.3), 8.84(1H, br d,J=2.4) Ia-15 172-173° C., ¹H-NMR(CDCl₃)δ5.11(1H, s), 5.17(2H, s),5.75(1H, s), 6.93(2H, d, J=8.5), 6.95-7.03(2H, m), 7.11(1H, d, J=2.0),7.38-7.45(5H, m), 7.62(1H, d, J=8.1), 7.67(1H, d, J=8.1), 7.96(2H, d,J=8.5)

 

TABLE 89 Ia-16 159-161° C., ¹H-NMR(CDCl₃)δ1.77(3H, s), 1.83(3H, s),4.63(2H, d, J=6.8), 5.02(1H, s), 5.52(1h, br t, J=6.8), 5.75(1H, s),6.92(2H, d, J=8.5), 6.94(1H, d, J=8.3), 6.97(1H, dd, J=2.2, 8.3),7.08(1H, d, J=2.2), 7.62(1H, d, J=8.1), 7.66(1H, d, J=8.1), 7.95(2H, d,J=8.5) Ia-17 134-134.5° C., ¹H-NMR(CDCl₃)δ3.13(3H, s), 3.18(3H, s),5.20(2H, s), 7.16(1H, d, J=8.5), 7.37-7.50(9H, m), 7.71 and 7.74(each1H, ABq, J=8.1), 8.10(2H, d, J=8.8) Ia-18 99-100° C.,¹H-NMR(CDCl₃)δ1.77(3H, s), 1.82(3H, s), 3.19(3H, s), 3.24(3H, s),4.66(2H, d, J=6.8), 5.51(1h, br t, J=6.8), 7.10(1H, d, J=8.5),7.38-7.48(4H, m), 7.71 and 7.74(each 1H, ABq, J=8.1), 8.10(2H, d, J=8.8)Ia-21 215-216° C., ¹H-NMR(CDCl₃-DMSO-d₆)δ1.77(3H, s), 1.82(3H, s),2.35(3H, s), 4.63(2H, d, J=6.8), 5.54(1H, br t, J=6.8), 6.51(1H, s),6.79(1H, dd, J=2.2, 8.1), 6.93-6.96(4H, m), 7.52(1H, s), 7.87(2H, d,J=8.8), 8.43(1H, s), 8.79(1H, s) Ia-22 203-204° C.,¹H-NMR(CDCl₃)δ1.76(3H, s), 1.80(3H, s), 2.37(3H, s), 3.89(3H, s),4.64(2H, d, J=6.8), 5.56(1H, br t, J=6.8), 6.20(1H, br s), 6.86-6.89(2H,m), 6.89(2H, d, J=8.8), 6.97(1H, d, J=8.5), 7.55(1H, s), 7.88(2H, d,J=8.8), 8.48(1H, s) Ia-23 140-141° C., ¹H-NMR(CDCl₃)δ2.39(3H, s),3.17(3H, s), 5.18(2H, s), 5.78(1H, s), 6.83(1H, dd, J=2.2, 8.3),6.98(1H, d, J=2.2), 7.03(1H, d, J=8.3), 7.40(2H, d, J=8.8),7.41-7.47(5H, m), 7.59(1H, s), 8.07(2H, d, J=8.8), 8.50(1H, s) Ia-24156-157° C., ¹H-NMR(CDCl₃)δ2.39(3H, s), 3.13(3H, s), 3.18(3H, s),5.20(2H, s), 7.18(1H, d, J=8.5), 7.26(1H, dd, J=2.0, 8.5),7.36-7.49(8H,,m), 7.61(1H, s), 8.07(2H, d, J=90.), 8.50(1H, s) Ia-25111-112° C., ¹H-NMR(CDCl₃)δ1.78(3H, s), 1.83(3H, s), 2.39(3H, s),3.18(3H, s), 3.24(3H, s), 4.65(2H, d, J=6.8), 5.51(1H, br t, J=6.8),7.11(1H, d, J=8.5), 7.26(1H, dd, J=2.2, 8.5), 7.34(1H, d, J=2.2),7.40(2H, d, J=8.8), 7.60(1H, s), 8.07(2H, d, J=8.8), 8.50(1H, s) Ia-26124-127° C., ¹H-NMR(CDCl₃)δ1.77(3H, s), 1.80(3H, s), 2.39(3H, s),3.18(3H, s), 3.90(3H, s), 4.65(2H, d, J=6.8), 5.57(1H, br t, J=6.8),6.87-6.91(2H, m), 6.98(1H, d, J=8.3), 7.40(2H, d, J=8.8), 7.60(1H, s),8.08(2H, d, J=8.8), 8.53(1H, s) Ia-27 213-214° C.,¹H-NMR(CDCl₃)δ2.58(3H, s), 5.21(2H, s), 5.87(1H, s), 7.06-7.18(5H, m),7.42-7.49(7H, m), 8.29(1H, brs), 8.86(1H, brs), 9.01(1H, brs) Ia-28198-199° C., ¹H-NMR(CDCl₃)δ1.77(3H, s), 1.82(3H, s), 2.42(3H, s),4.63(2H, d, J=6.7), 5.51(1H, t, J=6.7), 5.68(1H, s), 5.77(1H, s),6.87(2H, d, J=7.8), 6.96(1H, d, J=8.5), 7.10(1H, dd, J=8.5, 2.4),7.21(1H, d, J=2.4), 7.44(2H, d, J=7.8) 7.71(1H, d, J=2.4), 8.68(1H, d,J=2.4), Ia-31 198-199° C., ¹H-NMR(CDCl₃)δ2.53(3H, s), 3.14(3H, s),3.21(3H, s), 5.21(2H, s), 7.22(1H, d, J=8.5), 7.39-7.49(7H, m),7.55-7.62(2H, m), 7.73(2H, d, J=9.2), 8.05(1H, brs), 8.84(1H, brs) Ia-32142-144° C., ¹H-NMR(CDCl₃)δ1.78(3H, s), 1.82(3H, s), 2.43(3H, s),3.17(3H, s), 3.24(3H, s), 4.65(2H, d, J=6.7), 5.50(1H, br t, J=6.7),7.12(1H, d, J=8.5), 7.40(2H, dd, J=6.7, 1.8), 7.52(1H, dd, J=8.6, 2.4),7.57(1H, s) 7.64(2H, d, J=8.5), 7.74(1H, s) 8.70(1H, d, J=2.5)

 

TABLE 90 Ia-35 152-154° C., ¹H-NMR(CDl₃)δ1.77(3H, s), 1.83(3H, s),2.59(3H, s), 4.12(2H, d, J=7.3), 5.53(1H, t, J=7.3), 5.77(1H, brs),6.79-6.95(5H, m), 7.49(1H, d, J=8.0), 7.55(1H, d, J=8.0), 7.88(2H, d,J=8.5) Ia-38 109-112° C., ¹H-NMR(CDCl₃)δ2.60(3H, s), 3.12(3H, s),3.16(3H, s), 5.19(2H, s), 7.15(1H, d, J=8.5), 7.27(1H, dd, J=7.8, 1.8),7.35-7.50(8H, m), 7.59(2H, s), 8.09(2H, d, J=9.2) Ia-39 oil, 1.78(3H,s), ¹H-NMR(CDCl₃)δ1.82(3H, s), 2.60(3H, s), 3.17(3H, s), 3.24(3H, s),4.65(2H, d, J=6.7), 5.51(1H, br t, J=6.7), 7.09(1H, d, J=8.6),7.24-7.27(1H, m), 7.34-7.35(2H, m), 7.40(1H, d, J=8.6) 7.59(2H, s),8.09(2H, d, J=9.2) Ia-42 175-176° C., ¹H-NMR(CDCl₃)δ1.77(3H, s),1.83(3H, s), 2.32(3H, s), 2.54(3H, s), 4.63(2H, d, J=6.8), 5.52(1H,brs), 5.53(1H, t, J=6.8), 5.75(1H, brs), 6.80-6.84(3H, m), 6.93(1H, d,J=7.8), 6.95(1H, d, J=1.8), 7.38-7.41(3H, m) Ia-43 177-178° C.,¹H-NMR(CDCl₃)δ1.77(3H, s), 1.79(3H, s), 2.32(3H, s), 2.56(3H, s),3.90(3H, s), 4.64(2H, d, J=6.8), 5.56(1H, t, J=6.8), 6.75(2H, d, J=8.5),6.87-6.97(3H, m), 7.33(2H, d, J=8.5), 7.43(1H, s) Ia-45 79-81° C.,¹H-NMR(CDCl₃)δ2.33(3H, s), 2.53(3H, s), 3.16(3H, s), 5.18(2H, s),5.75(1H, s), 6.83(1H, dd, J=7.8, 1.8), 6.98(1H, d, J=1.8), 7.00(1H, d,J=8.5), 737-7.55(8H, m), 7.63(2H, d, J=8.5) Ia-46 163-164° C.,¹H-NMR(CDCl₃)δ2.34(3H, s), 2.54(3H, s), 3.13(3H, s), 3.17(3H, s),5.19(2H, s), 7.15(1H, d, J=8.5), 7.27(1H, dd, J=8.5, 2.5), 7.35-7.50(9H,m), 7.62(2H, d, J=8.5) Ia-47 oil, ¹H-NMR(CDCl₃)δ1.77(3H, s), 1.82(3H,s), 2.34(3H, s), 2.54(3H, s), 3.17(3H, s), 3.23(3H, s), 4.66(2H, d,J=7.3), 5.51(1H, br t, J=7.3), 7.08(1H, d, J=8.6), 7.26(1H, dd, J=8.6,2.4), 7.35(1H, d, J=2.4), 7.39(2H, d, J=8.6), 7.43(1H, s), 7.64(2H, d,J=8.6) Ia-48 149-150° C., ¹H-NMR(CDCl₃)δ1.77(3H, s), 1.80(3H, s),2.35(3H, s), 2.54(3H, s), 3.17(3H, s), 3.90(3H, s), 4.64(2H, d, J=6.8),5.57(1H, t, J=6.8), 6.87(1H, s), 6.88-6.98(2H, m), 7.39(2H, d, J=8.5),7.44(1H, s), 7.63(2H, d, J=8.5) Ia-65 237-239° C.,¹H-NMR(CDCl₃-CD₃OD)δ3.16(3H, s), 5.21(2H, s), 6.96(2H, d, J=8.6),7.20(1H, d, J=9.3), 7.38-7.51(5H, m), 7.72(1H, br d, J=8.3),7.90-7.95(3H, m), 8.80(1H, br d, J=2.4) Ia-66 152-153° C.,¹H-NMR(CDCl₃)δ1.76(3H, s), 1.81(3H, s), 4.63(2H, d, J=6.8), 5.51(1H, brt, J=6.8), 5.59(1H, br s), 5.75(1H, s), 6.95(2H, d, J=8.6), 6.97(1H, d,J=8.3), 7.50(2H, d, J=8.6), 7.56(1H, dd, J=2.2, 8.3), 7.59(1H, d,J=2.2), 7.69(1H, dd, J=0.7, 8.3), 7.86(1H, 2.4, 8.3), 8.83(1H, dd,J=0.7, 2.4) Ia-68 167-168° C., ¹H-NMR(CDCl₃)δ3.13(3H, s), 3.20(3H, s),5.21(2H, s), 7.18(1H, d, J=8.3), 7.38-7.48(7H, m), 7.67(2H, d, J=8.8),7.76(1H, br d, J=8.3), 7.91(1H, dd, J=2.4, 8.3), 7.99-8.03(2H, m),8.85(1H, br d, J=2.4) Ia-69 151-152.5° C., ¹H-NMR(CDCl₃)δ1.77(3H, s),1.81(3H, s), 3.20(3H, s), 3.24(3H, s), 4.66(2H, d, J=6.8), 5.50(1H, brt, J=6.8), 7.12(1H, d, J=9.3), 7.42(2H, d, J=8.5), 7.67(2H, d, J=8.5),7.76(1H, br d, J=8.3), 7.90(1H, dd, J=2.4, 8.3), 8.00-8.03(2H, m),8.85(1H, br d, J=2.4) Ia-71 220-221° C.¹H-NMR(CDCl₃)δ2.57(3H, s),3.51(2H, brs), 5.18(2H, s), 7.14(1H, d, J=7.3), 7.15-7.62(11H, m),8.11(1H, d, J=1.8), 8.78(1H, d, J=1.8)

 

TABLE 91 Ia-73 180-181° C., ¹H-NMR(CDCl₃)δ1.74(3H, s), 1.79(3H, s),2.42(3H, s), 4.61(2H, d, J=6.8), 5.50(1H, t, J=6.8), 6.84-6.96(5H, m),7.05(1H, dd, J=7.8, 1.8), 7.14(1H, d, J=1.8), 7.44(2H, d, J=9.2),7.71(1H, d, J=1.8) 8.65(1H, d, J=1.8), Ia-75 164-165° C.,¹H-NMR(CDCl₃)δ2.53(3H, s), 3.13(3H, s), 3.21(3H, s), 5.19(2H, s),7.16(1H, d, J=7.3), 7.32-7.50(7H, m), 7.61(2H, dd, J=8.5, 2.4), 7.70(2H,d, J=7.3), 7.79(1H, d, J=1.8) 8.76(1H, d, J=1.8) Ia-76 151-152°C.¹H-NMR(CDCl₃)δ1.77(3H, s), 1.81(3H, s), 2.48(3H, s), 3.20(3H, s),3,21(3H, s), 4.65(2H, d, J=6.8), 5.50(1H, t, J=6.8), 7.11(1H, d, J=7.9),7.41(2H, d, J=9.2), 7.55(1H, dd, J=7.8, 1.8), 7.58(1H, s), 7.66(2H, d,J=7.9), 7.74(1H, d, J=1.8) 8.71(1H, d, J=1.8), Ia-79 189-191° C.,¹H-NMR(CDCl₃)δ2.34(3H, s), 5.18(2H, s), 5.29(1H, br s), 5.71(1H, s),6.83(1H, dd, J=2.2, 8.3), 6.92(2H, d, J=8.6), 7.03(1H, d, J=8.3),7.23(2H, d, J=8.6), 7.37-7.47(5H, m), 7.54(1H, s), 7.55(1H, dd, J==2.2,8.3), 7.60(2H, d, J=2.2), 8.45(1H, s) Ia-80 165-166° C.,¹H-NMR(CDCl₃)δ1.76(3H, s), 1.81(3H, s), 2.35(3H, s), 4.63(2H, d, J=6.8),5.51(1H, br t, J=6.8), 5.75(1H, s), 6.19(1H, br s), 6.92(2H, d, J=8.8),6.96(1H, d, J=8.8), 7.21(2H, d, J=8.8), 7.52-7.57(3H, m), 8.44(1H, s)Ia-82 189-190° C., ¹H-NMR(CDCl₃)δ2.35(3H, s), 3.13(3H, s), 3.22(3H, s),5.20(2H, s), 7.18(1H, d, J=9.0), 7.36-7.49(9H, m), 7.58(1H, s),7.99-8.02(2H, m), 8.46(1H, s) Ia-83 169-170° C., ¹H-NMR(CDCl₃)δ1.77(3H,s), 1.81(3H, s), 2.35(3H, s), 3.22(3H, s), 3.24(3H, s), 4.66(2H, d,J=6.8), 5.50(1H, br t, J=6.8), 7.11(1H, d, J=8.6), 7.40(4H, s), 7.58(1H,s), 7.96(1H, d, J=2.2), 8.00(1H, dd, J==2.2, 8.6), 8.45(1H, s) Ia-85143-146° C., ¹H-NMR(CDCl₃)δ2.53(3H, s), 5.03(1H, brs), 5.18(2H, s),5.72(1H, s), 6.92(2H, dd, J=7.8, 1.8), 7.02(1H, d, J=6.8), 7.23(2H, dd,J=7.3, 1.8), 7.33-7.48(5H, m), 7.49-7.60(3H, m), 7.67(1H, d, J=1.8)Ia-87 168-169° C., ¹H-NMR(CDCl₃)δ1.76(3H, s), 1.81(3H, s), 2.56(3H, s),4.63(2H, d, J=6.8), 4.84(1H, s), 5.51(1H, t, J=6.8), 5.70(1H, s),6.91(2H, d, J=8.5), 6.95(1H, d, J=8.5), 7.22(2H, s), 7.51(2H, s),7.55(1H, dd, J==8.5, 2.4), 7.62(1H, d, J=2.4) Ia-89 174-175° C.,¹H-NMR(CDCl₃)δ2.56(3H, s), 3.13(3H, s), 3.21(3H, s), 5.20(2H, s),7.15(1H, d, J=8.5), 7.29-7.48(9H, m), 7.56(2H, s), 7.99(1H, dd, J=8.5,2.4), 8.03(1H, d, J=2.4) Ia-90 141-142° C., ¹H-NMR(CDCl₃)δ1.77(3H, s),1.81(3H, s), 2.56(3H, s), 3.21(3H, s), 3.24(3H, s), 4.65(2H, d, J=6.8),5.50(1H, t, J=6.8), 7.10(1H, d, J=8.6), 7.36-7.43(4H, m), 7.55(2H, d,J=1.2), 7.98(1H, dd, J=8.6, 2.4), 8.01(1H, d, J=1.2) Ia-93 118-121° C.,¹H-NMR(CDCl₃)δ2.36(3H, s), 2.51(3H, s), 3.10(3H, s), 5.10(1H, brs),5.18(2H, s), 6.90(2H, d, J=8.6), 7.14(1H, d, J=8.6), 7.21-7.48(8H, m),7.52(1H, dd, J=8.6, 1.8), 7.58(1H, d, J=1.8) Ia-94 168-169° C.,¹H-NMR(CDCl₃)δ1.76(3H, s), 1.81(3H, s), 2.33(3H, s), 2.51(3H, s),4.61(2H, d, J=6.8), 5.32(1H, brs), 5.51(1H, t, J=6.8), 5.73(1H, s),6.87-6.95(3H, m), 7.04(1H, dd, J=8.5, 1.8), 7.14(1H, d, J=1.8),7.21-7.24(2H, m), 7.37(1H, s) Ia-96 140-141° C., ¹H-NMR(CDCl₃)δ2.38(3H,s), 2.50(3H, s), 3.11(3H, s), 3.21(3H, s), 5.19(2H, s), 7.16(1H, d,J=8.5), 7.33-7.51(10H, m), 7.55(1H, dd, J=7.8, 1.8), 7.62(1H, d, J=1.8)

 

TABLE 92 Ia-97 106-107° C., ¹H-NMR(CDl₃)δ1.77(3H, s), 1.81(3H, s),2.38(3H, s), 2.51(3H, s), 3.20(3H, s), 3.21(3H, s), 4.64(2H, d, J=6.8),5.49(1H, t, J=6.8), 7.10(1H, d, J=8.0), 7.35-7.44(5H, m), 7.51-7.65(2H,m) Ia-125 121-122° C., ¹H-NMR(CDCl₃)δ2.38(3H, s), 3.90(3H, s), 4.03(3H,s), 5.21(2H, s), 6.77(1H, dd, J=2.0, 8.3), 6.82(1H, d, J=2.0), 6.97(1H,d, J=8.3), 7.32-7.49(8H, m), 8.46-8.49(2H, m) Ia-127 110-111° C.,¹H-NMR(CDCl₃)δ2.39(3H, s), 4.03(3H, s), 5.11(2H, s), 7.06(2H, d, J=8.5),7.22(2H, d, J=8.5), 7.34-7.51(8H, m), 8.44-8.50(2H, m) Ia-128 115-116°C., ¹H-NMR(CDCl₃)δ2.38(3H, s), 4.03(3H, s), 5.07(2H, s), 7.06(2H, d,J=9.2), 7.21(4H, d, J=9.2), 7.36(2H, d, J=8.5), 7.45-7.51(3H, m),8.46-8.50(2H, m) Ia-129 129-130° C., ¹H-NMR(CDCl₃)δ1.77(3H, s), 1.82(3H,s), 2.39(3H, s), 4.03(3H, s), 4.56(2H, d, J=6.7), 5.55(1H, br t, J=6.7),7.00(2H, d, J=8.5), 7.21(2H, d, J=8.5), 7.46-7.51(3H, m), 8.46-8.50(2H,m) Ia-131 121-122° C., ¹H-NMR(CDCl₃)δ2.39(3H, s), 4.03(3H, s), 5.16(2H,s), 5.75(1h, s), 6.76(1H, dd, J=2.2, 8.3), 6.90(1H, d, J=2.2), 7.0l(1H,d, J=8.1), 7.38-7.5(8H, m), 8.46-8.50(2H, m) Ia-132 142-143° C.,¹H-NMR(CDCl₃)δ2.29(3H, s), 2.41(3H, s), 4.02(3H, s), 5.14(2H, s),7.02(1H, d, J=1.2), 7.05-7.11(2H, m), 7.33-7.49(8H, m), 8.45-8.50(2H, m)Ia-133 161.5-162.5° C., ¹H-NMR(CDCl₃)δ2.42(3H, s), 3.11(3H, s), 4.03(3H,s), 5.18(2H, s), 7.14(1H, d, J=8.6), 7.21(1H, dd, J=2.0, 8.6), 7.31(1H,d, J=2.0), 7.37-7.50(8H, m), 8.46-8.49(2H, m) Ia-134 142-143° C.,¹H-NMR(CDCl₃)δ2.39(3H, s), 4.03(3H, s), 5.23(2H, s), 7.15(1H, d, J=8.5),7.17-7.25(2H, m), 7.33-7.51(8H, m), 8.45-8.50(2H, m) Ia-135 132-133° C.,¹H-NMR(CDCl₃)δ2.37(311, s), 4.03(3H, s), 4.94(2H, s), 6.98(1H, d,J=8.6), 7.15(1H, dd, J=1.8, 8.6), 7.17(1H, d, J=1.8), 7.33-7.60(11H, m),7.87(2H, d, J=7.3), 8.45-8.59(2H, m) Ia-136 127-128° C.,¹H-NMR(CDCl₃)δ2.40(3H, s), 2.42(3H, s), 4.04(3H, s), 5.14(2H, s),5.70(1H, s), 6.79(1H, dd, J=1.8, 7.9), 6.90(1H, d, J=1.8), 7.05(1H, d,J=7.9), 7.22-7.36(3H, m), 7.40(1H, d, J=6.7), 7.43-7.55(311, m),8.44-8.50(2H, m) Ia-137 87-89° C., ¹H-NMR(CDCl₃)δ2.39(3H, s), 2.41(3H,s), 4.03(3H, s), 5.12(2H, s), 5.73(1H, s), 6.76(1H, dd, J=1.8, 7.9),6.90(1H, d, J=1.8), 7.01(1H, d, J=7.9), 7.18-7.36(4H, m), 7.43-7.53(3H,m), 8.46-8.52(2H, m) Ia-138 114-115° C., ¹H-NMR(CDCl₃)δ2.39(6H, s),4.02(3H, s), 5.10(2H, s), 5.74(1H, s), 6.75(1H, dd, J=2.0, 8.3),6.89(1H, d, J=2.0), 7.01(1H, d, J=8.3), 7.24(2H, d, J=8.6), 7.36(2H, d,J=8.6), 7.45-7.50(3H, m), 8.46-8.50(2H, m) Ia-139 192-193° C.,¹H-NMR(CDCl₃)δ2.42(3H, s), 2.43(3H, s), 3.06(3H, s), 4.04(3H, s),5.16(2H, s), 7.15-7.33(6H, m), 7.41-7.50(4H, m), 8.46-8.51(2H, m) Ia-140151-152° C., ¹H-NMR(CDCl₃)δ2.39(3H, s), 2.42(3H, s), 3.12(3H, s),4.03(3H, s), 5.14(2H, s), 7.14(1H, d, J=8.5), 7.18-7.31(6H, m),7.46-7.50(3H, m), 8.45-8.50(2H, m) Ia-141 188-189° C.,¹H-NMR(CDCl₃)δ2.39(3H, s), 2.41(3H, s), 3.11(3H, s), 4.03(3H, s),5.13(2H, s), 7.14(1H, d, J=8.6), 7.20(1H, dd, J=2.2, 8.6), 7.22(2H, d,J=8.0), 7.30(1H, d, J=2.2), 7.36(2H, d, J=8.0), 7.47-7.50(3H, m),8.46-8.49(2H, m)

 

TABLE 93 Ia-142 166-167° C., ¹H-NMR(CDCl₃)δ2.39(3H, s), 3.91(3H, s),4.03(3H, s), 5.15(2H, s), 6.18(1H, s), 6.75(1H, dd, J=1.8, 7.9),6.89(1H, d, J=2.4), 6.97(1H, d, J=7.9), 7.03(1H, d, J=7.9),7.34-7.49(5H, m), 8.46-8.50(2H, m) Ia-143 166-167° C.,¹H-NMR(CDCl₃)δ2.39(3H, s), 3.84(3H, s), 4.03(3H, s), 5.13(2H, s),5.74(1H, s), 6.75(1H, dd, J=1.8, 8.5), 6.89(1H, d, J=1.8), 6.90-7.05(4H,m), 7.34(1H, d, J=7.9), 7.44-7.50(3H, m), 8.45-8.50(2H, m) Ia-144125-126° C., ¹H-NMR(CDCl₃)δ2.39(3H, s), 3.85(3H, s), 4.03(3H, s),5.08(2H, s), 5.70(1H, s), 6.76(1H, dd, J=1.8, 7.9), 6.89(1H, d, J=8.5),6.96(2H, d, J=8.5), 7.02(1H, d, J=7.9), 7.38(2H, d, J=8.5),7.44-7.50(3H, m), 8.45-8.50(2H, m) Ia-145 193-195° C.,¹H-NMR(CDCl₃)δ2.42(3H, s), 3.13(3H, s), 3.87(3H, s), 4.03(3H, s),5.21(2H, s), 6.94(1H, d, J=7.9), 6.98-7.04(1H, m), 7.19-7.21(2H, m),7.30(1H, d, J=1.8), 7.36(1H, d, J=7.9) 7.45-7.50(4H, m), 8.45-8.50(2H,m) Ia-146 166-167° C., ¹H-NMR(CDCl₃)δ2.41(3H, s), 3.15(3H, s), 3.84(3H,s), 4.03(3H, s), 5.16(2H, s), 6.91(1H, d, J=8.5), 7.02-7.06(2H, m),7.12(1H, d, J=8.5), 7.20(1H, dd, J=1.8, 8.5), 7.30(1H, d, J=1.8),7.35(1H, d, J=7.9) 7.45-7.49(3H, m), 8.45-8.50(2H, m) Ia-147 171-172°C.¹H-NMR(CDCl₃)δ2.41(3H, s), 3.09(3H, s), 3.84(3H, s), 4.03(3H, s),5.10(2H, s), 6.94(2H, d, J=8.5), 6.97-7.23(2H, m), 7.29(1H, d, J=1.8),7.39(2H, d, J=8.5), 7.45-7.49(3H, m), 8.45-8.49(2H, m) Ia-148 177-179°C., ¹H-NMR(CDCl₃)δ2.39(3H, s), 4.03(3H, s), 5.27(2H, s), 6.72(1H, dd,J=2.4, 8.5), 6.93(1H, d, J=1.8), 7.12(1H, d, J=7.9), 7.31-7.36(2H, m),7.46-7.49(3H, m), 7.78(1H, dt, J=1.8, 7.3), 8.46-8.50(2H, m), 8.68(1H,d, J=4.9), 9.76(1H, s) Ia-149 221-212° C., ¹H-NMR(CDCl₃)δ2.39(3H, s),4.03(3H, s), 5.19(2H, s), 5.69(1H, s), 6.78(1H, dd, J=1.8, 7.9),6.92(1H, d, J=2.4), 7.01(1H, d, J=8.5), 7.35-7.40(1H, m), 7.45-7.51(3H,m), 7.80(1H, d, J=7.9), 8.46-8.50(2H, m), 8.65(1H, d, J=4.9), 8.72(1H,s) Ia-150 222-224° C., ¹H-NMR(CDCl₃)δ2.39(3H, s), 4.03(3H, s), 5.19(2H,s), 6.08(1H, s), 6.75(1H, dd, J=1.8, 7.9), 6.92(1H, d, J=6.7), 6.94(1H,s), 7.35(2H, d, J=6.1), 7.45-7.51(3H, m), 8.25-8.50(2H, m), 8.65(2H, d,J=5.5) Ia-151 195-197° C., ¹H-NMR(CDCl₃)δ2.41(3H, s), 3.23(3H, s),4.03(3H, s), 5.32(2H, s), 7.13(1H, d, J=8.5), 7.20(1H, dd, J=2.4, 8.5),7.26-7.33(2H, m), 7.46-7.50(3H, m), 7.62(1H, d, J=7.3), 7.78(1H, dt,J=1.8, 7.9), 8.45-8.50(2H, m), 8.62(1H, d, J=4.9) Ia-152 173-174° C.,¹H-NMR(CDCl₃)δ2.42(3H, s), 3.13(3H, s), 4.03(3H, s), 5.21(2H, s),7.15(1H, d, J=7.9), 7.21(1H, d, J=1.8), 7.31(1H, d, J=1.8),7.36-7.41(1H, m), 7.47-7.89(3H, m), 8.46-8.50(2H, m), 8.73(1H, s),8.65(1H, d, J=4.9), 8.73(1H, s) Ia-153 186-187° C.,¹H-NMR(CDCl₃)δ2.41(3H, s), 3.20(3H, s), 4.03(3H, s), 5.22(2H, s),7.06(1H, d, J=8.5), 7.21(1H, dd, J=1.8, 8.5), 7.32(1H, d, J=2.4),7.42(1H, d, J=6.1), 7.47-7.50(3H, m), 8.45-8.50(2H, m), 8.68(2H, d,J=4.9) Ia-154 112-113° C., ¹H-N-(CDCl₃)δ2.37(3H, s), 3.16(2H, t, J=6.7),4.02(3H, s), 4.32(2H, t, J=6.7), 5.55(1H, s), 6.74(1H, dd, J=1.8, 8.5),6.85(1H, d, J=1.8), 6.93(1H, d, J=8.5), 7.25-7.39(5H, m), 7.45-7.49(3H,m), 8.45-8.49(2H, m)

 

TABLE 94 Ia-155 169-170° C., ¹H-NMR(CDCl₃)δ2.39(3H, s), 2.88(3H, s),3.18(2H, t, J=6.7), 4.02(3H, s), 4.35(2H, t, J=6.7), 7.07(1H, d, J=8.5),7.19(1H, dd, J=1.8, 7.9), 7.25-7.38(6H, m), 7.46-7.49(3H, m),8.44-8.49(2H, m) Ia-156 117-119° C., ¹H-NMR(CDCl₃)δ1.77(3H, s), 1.83(3H,s), 2.39(3H, s), 4.03(3H, s), 4.62(2H, d, J=6.8), 5.52(1H, br t, J=6.8),5.75(1H, s), 6.75(1H, dd, J=2.2, 8.3), 6.87(1H, d, J=2.2), 6.94(1H, d,J=8.3), 7.45-7.50(3H, m), 8.46-8.49(2H, m) Ia-157 121-124° C.,¹H-NMR(CDCl₃)δ1.77(3H, s), 1.82(3H, s), 2.42(3H, s), 3.23(3H, s),3.40(3H, s), 4.63(2H, d, J=6.8), 5.51(1H, br t, J=6.8), 7.07(1H, d,J=8.6), 7.19(1H, dd, J=2.0, 8.6), 7.28(1H, d, J=2.0), 7.45-7.50(3H, m),8.45-8.49(2H, m) Ia-159 79-80° C., ¹H-NMR(CDCl₃)δ1.75(3H, s), 1.76(3H,s), 2.38(3H, s), 2.54(2H, q, J=6.7), 4.03(3H, s), 4.08(2H, t, J=6.7),5.23(1H, t, J=7.3), 5.71(1H, s), 6.74(1H, dd, J=1.8, 7.9), 6.87(1H, d,J=1.8), 6.92(1H, d, J=7.9), 7.44-7.51(3H, m), 8.45-8.50(2H, m) Ia-160152-153° C., ¹H-NMR(CDCl₃)δ1.69(3H, s), 1.74(3H, s), 2.41(3H, s),2.56(2H, q, J=6.7), 3.21(3H, s), 4.03(3H, s), 4.08(2H, t, J=6.7),5.22(1H, t, J=6.7), 7.06(1H, d, J=7.9), 7.20(1H, dd, J=1.8, 7.9),7.28(1H, d, J=1.8), 7.46-7.50(3H, m), 8.45-8.50(2H, m) Ia-162200.5-201.5° C., ¹H-NMR(CDCl₃)δ2.38(3H, s), 3.11(3H, s), 4.01(3H, s),5.17(2H, s), 5.38(1H, s), 6.90(2H, d, J=8.8), 7.13(1H, d, J=8.5),7.19(1H, dd, J=2.0, 8.5), 7.29(1H, d, J=2.0), 7.37-7.49(5H, m), 8.37(2H,d, J=8.8) Ia-163 163-168° C., ¹H-NMR(CDCl₃)δ1.77(3H, s), 1.83(3H, s),2.36(3H, s), 4.01(3H, s), 4.62(2H, d, J=6.6), 5.53(1H, br t, J=6.6),5.58(1H, br), 5.74(1H, br s), 6.73(1H, dd, J=2.0, 8.3), 6.86(1H, d,J=2.0), 6.89(2H, d, J=8.8), 6.93(1H, d, J=8.3), 8.37(2H, J=8.8) Ia-167185.5-186.5° C., ¹H-NMR(CDCl₃)δ2.41(3H, s), 3.11(3H, s), 3.18(3H, s),4.02(3H, s), 5.18(2H, s), 7.15(1H, d, J=8.3), 7.21(1H, dd, J=2.0, 8.3),7.30(1H, d, J=2.0), 7.36-7.49(7H, m), 8.54(2H, d, J=8.8) Ia-168 138-139°C., ¹H-NMR(CDCl₃)δ1.77(3H, s), 1.82(3H, s), 2.41(3H, s), 3.18(3H, s),3.22(3H, s), 4.02(3H, s), 4.64(2H, d, J=6.8), 5.51(1H, br t, J=6.8),7.08(1H, d, J=8.5), 7.19(1H, dd, J=2.0, 8.5), 7.28(1H, d, J=2.0),7.39(2H, d, J=9.0), 8.54(2H, J=9.0) Ia-173 202-204° C.,¹H-NMR(CDCl₃)δ2.40(3H, s), 2.55(3H, s), 3.11(3H, s), 4.02(3H, s),5.17(2H, s), 7.14(1H, d, J=8.5), 7.20(1H, dd, J=2.0, 8.5), 7.30(1H, d,J=2.0), 7.33(2H, br d, J=8.6), 7.37-7.50(5H, m), 8.40(2H, br d, J=8.6)Ia-175 205-206° C., ¹H-NMR(CDCl₃)δ2.44(3H, s), 3.10(3H, s), 3.12(3H, s),4.05(3H, s), 5.18(2H, s), 7.16(1H, d, J=8.5), 7.21(1H, dd, J=2.0, 8.5),7.31(1H, d, J=2.0), 7.37-7.50(5H, m), 8.05(2H, br d, J=8.6), 8.68(2H, brd, J=8.6) Ia-176 178-179° C., ¹H-NMR(CDCl₃)δ2.40(3H, s), 3.11(3H, s),4.01(3H, s), 5.17(2H, s), 7.12-7.22(4H, m), 7.29(1H, d, J=2.0),7.37-7.50(5h, m), 8.48(2H, dd, J=5.6, 9.0) Ia-177 127-128° C.,¹H-NMR(CDCl₃)δ1.77(3H, s), 1.83(3H, s), 2.37(3H, s), 4.01(3H, s),4.62(2H, d, J=6.8), 5.53(1H, br t, J=6.8), 5.74(1H, s), 6.74(1H, dd,J=2.0, 8.3), 6.86(1H, d, J=2.0), 6.94(1H, d, J=8.3), 7.14(2H, d, J=8.8),8.48(2H, dd, J=5.6, 8.8)

 

TABLE 95 Ia-178 143-144° C., ¹H-NMR(CDl₃)δ1.77(3H, s), 1.82(3H, s),2.40(3H, s), 3.23(3H, s), 4.02(3H, s), 4.63(2H, d, J=6.8), 5.51(1H, brt, J=6.8), 7.05-7.20(4H, m), 7.27(1H, d, J=2.2), 8.48(2H, dd, J=5.6,9.0) Ia-179 118-120° C., ¹H-NMR(CDCl₃)δ2.43(3H, s), 3.12(3H, s),4.05(3H, s), 5.18(2H, s), 7.15(1H, d, J=8.6), 7.21(1H, dd, J=2.0, 8.6),7.31(1H, d, J=2.0), 7.38-7.50(5H, m), 7.60(1H, br t, J=7.8), 7.73(1H, brd, J=7.8), 8.67(1H, br d, J=7.8), 8.75(1H, br s) Ia-180 114-115 CC,¹H-NMR(CDCl₃)δ1.77(3H, s), 1.83(3H, s), 2.40(3H, s), 4.04(3H, s),4.63(2H, d, J=6.8), 5.53(1H, br t, J=6.8), 5.74(1H, s), 6.75(1H, dd,J=2.0, 8.3), 6.87(1H, d, J=2.0), 6.95(1H, d, J=8.3), 7.60(1H, t, J=7.8),7.72(1H, br d, J=7.8), 8.67(1H, br d, J=7.8), 8.75(1H, s) Ia-181102-103° C., ¹H-NMR(CDCl₃)δ1.77(3H, s), 1.82(3H, s), 2.43(3H, s),3.23(3H, s), 4.05(3H, s), 4.64(2H, d, J=6.8), 5.51(1H, br t, J=6.8),7.08(1H, d, J=8.6), 7.20(1H, dd, J=2.2, 8.6), 7.28(1H, d, J=2.2),7.60(1H, t, J=7.6), 7.73(1H, d, J=7.6), 8.67(1H, d, J=7.6), 8.75(1H, s)Ia-182 155-156° C., ¹H-NMR(CDCl₃)δ2.41(3H, s), 4.06(3H, s), 5.17(2H, s),5.75(1H, s), 6.76(1H, dd, J=2.0, 8.3), 6.90(1H, d, J=2.0), 7.02(1H, d,J=8.3), 7.40-7.48(5H, m), 7.65(1H, t, J=8.1), 8.31(1H, ddd, J=1.2, 2.5,8.1), 8.83(1H, ddd, J=1.2, 1.5, 8.1), 9.31(1H, dd, J=1.5, 2.5) Ia-183160-167° C., ¹H-NMR(CDCl₃)δ2.44(3H, s), 3.12(3H, s), 4.06(3H, s),5.19(2H, s), 7.16(1H, d, J=8.5), 7.22(1H, dd, J=2.2, 8.5), 7.31(1H, d,J=2.2), 7.38-7.49(5H, m), 7.65(1H, t, J=8.1), 8.32(1H, ddd, J=1.2, 2.4,8.3), 8.83(1H, ddd, J=1.2, 1.5, 8.3), 9.31(1H, dd, J=1.5, 2.4) Ia-184153-155° C., ¹H-NMR(CDCl₃)δ2.40(3H, s), 3.11(3H, s), 4.02(3H, s),5.17(2H, s), 6.81(1H, ddd, J=1.2, 2.5, 7.8), 7.14(1H, d, J=8.5),7.20(1H, dd, J=2.2, 8.5), 7.27(1H, t, J=7.8), 7.30(1H, d, J=2.2),7.37-7.48(5H, m), 7.81(1H, dd, J=1.5, 2.5), 7.88(1H, ddd, J=1.2, 1.5,7.8) Ia-185 143-144° C., ¹H-NMR(CDCl₃)δ2.22(3H, s), 2.40(3H, s),3.11(3H, s), 4.03(3H, s), 5.17(2H, s), 7.14(1H, d, J=8.6), 7.21(1H, dd,J=2.0, 8.6), 7.30(1H, d, J=2.0), 7.31(1H, s), 7.37-7.48(6H, m), 7.91(1H,br d, J=8.1), 8.23(1H, br d, J=8.1), 8.35(1H, br s) Ia-186 171-172° C.,¹H-NMR(CDCl₃)δ2.40(3H, s), 3.05(3H, s), 3.12(3H, s), 4.02(3H, s),5.18(2H, s), 6.59(1H, br s), 7.14(1H, d, J=8.6), 7.20(1H, dd, J=2.0,8.6), 7.30(1H, d, J=2.0), 7.37-7.52(7H, m), 8.24(1H, br s), 8.31(1H, brd, J=6.8) Ia-187 165-167° C., ¹H-NMR(CDCl₃)δ1.77(3H, s), 1.83(3H, s),2.39(3H, s), 3.05(3H, s), 4.03(3H, s), 4.6(2H, d, J=6.8), 5.5(1H, br t,J=6.8), 5.74(1H, s), 6.45(1H, br s), 6.73(1H, dd, J=2.2, 8.3), 6.86(1H,d, J=2.2), 6.94(1H, d, J=8.3), 7.45-7.52(2H, m), 8.24(1H, m),8.30-8.34(1H, m) Ia-188 150-151° C., ¹H-NMR(CDCl₃)δ1.58(3H, s), 1.67(3H,s), 2.41(3H, s), 2.96(3H, s), 3.12(3H, s), 4.03(3H, s), 4.36(2H, d,J=7.3), 5.18(2H, s), 5.29(1H, br t, J=7.3), 7.15(1H, d, J=8.6), 7.20(1H,dd, J=2.0, 8.6), 7.29(1H, d, J=2.0), 7.37-7.48(7H, m), 8.42-8.45(2H, m)Ia-189 91-94° C., ¹H-NMR(CDCl₃)δ1.58(3H, s), 1.67(3H, s), 1.77(3H, s),1.83(3H, s), 2.38(3H, s), 2.96(3H, s), 4.02(3H, s), 4.36(2H, d, J=6.8),4.62(2H, d, J=6.8), 5.29(1H, br t, J=6.8), 5.52(1H, br t, J=6.8),5.76(1H, s), 6.73(1H, dd, J=2.2, 8.3), 6.86(1H, d, J=2.2), 6.94(1H, d,J=8.3), 7.45-7.51(2H, m), 8.42-8.46(2H, m)

 

TABLE 96 Ia-190 110-111° C., ¹H-NMR(CDCl₃)δ 1.58(3H, s), 1.67(3H, s),1.77(3H, s), 1.82(3H, s), 2.41(3H, s), 2.97(3H, s), 3.23(3H, s),4.02(3H, s), 4.36(2H, d, J=7.1), 4.64(2H, d, J=7.1), 5.29(1H, br t,J=7.1), 5.51(1H, br t, J=7.1), 7.08(1H, d, J=8.5), 7.19(1H, dd, J=2.0,8.5), 7.27(1H, d, J=2.0), 7.46-7.52(2H, m), 8.43(2H, m) Ia-191 131-132°C. Ia-192 171.5-172° C., ¹H-NMR(CDCl₃)δ2.40(3H, s), 3.11(3H, s),3.89(3H, s), 5.18(2H, s), 7.15(1H, d, J=8.6), 7.22(1H, dd, J=2.0, 8.6),7.30(1H, d, J=2.0), 7.38-7.50(5H, m), 7.56(1H, ddd, J=1.5, 7.6, 7.6),7.66(1H, ddd, J=1.5, 7.6, 7.6), 7.73(1H, dd, J=1.5, 7.6), 8.17(1H, dd,J=1.5, 7.6) Ia-194 249-251° C., ¹H-NMR(CDCl₃)δ2.27(3H, s), 2.45(3H, s),3.12(3H, s), 4.05(3H, s), 5.30(2H, s), 7.13-7.24(3H, m), 7.31(1H, d,J=2.0), 7.38-7.50(6H, m), 8.62(1H, dd, J=1.7, 8.3), 8.73(1H, br d,J=8.1), 13.18(1H, br s) Ia-195 180-181° C., ¹H-NMR(CDCl₃)δ1.77(3H, s),1.83(3H, s), 2.27(3H, s), 2.42(3H, s), 4.04(3H, s), 4.63(2H, d, J=6.8),5.53(1H, br t, J=6.8), 5.77(1H, s), 6.76(1H, dd, J=2.0, 8.3), 6.88(1H,d, J=2.0), 6.96(1H, d, J=8.3), 7.16(1H, ddd, J=1.2, 7.0, 8.1), 7.46(1H,ddd, J=1.7, 7.0, 8.5), 8.63(1H, dd, J=1.7, 8.1), 8.73(1H, br d, J=8.5),13.28(1H, br s) Ia-196 169-170° C., ¹H-NMR(CDCl₃)δ1.77(3H, s), 1.82(3H,s), 2.27(3H, s), 2.45(3H, s), 3.23(3H, s), 4.04(3H, s), 4.65(2H, d,J=6.8), 5.52(1H, br t, J=6.8), 7.16(1H, ddd, J=1.2, 7.3, 8.1), 7.22(1H,dd, J=2.2, 8.6), 7.29(1H, d, J=2.2), 7.47(1H, ddd, J=1.5, 7.3, 8.1),8.62(1H, dd, J=1.5, 8.1), 8.73(1H, br d, J=8.1), 13.21(1H, br s) Ia-197176-178° C., ¹H-NMR(CDCl₃)δ2.45(3H, s), 3.03(3H, s), 3.12(3H, s),4.05(3H, s), 5.18(2H, s), 7.14-7.24(3H, m), 7.30(1H, d, J=2.0),7.38-7.51(6H, m), 7.76(1H, dd, J=1.0, 8.3), 8.69(1H, dd, J=1.7, 8.1),13.19(1H, br s) Ia-199 157-158° C., ¹H-NMR(CDCl₃)δ1.36(3H, t, J=6.7),2.42(3H, s), 3.11(3H, s), 4.54(2H, q, J=6.7), 5.18(2H, s), 7.14(1H, d,J=7.9), 7.21(1H, dd, J=1.8, 8.5), 7.32(1H, d, J=2.4), 7.37-7.49(8H, m),8.43-8.48(2H, m) Ia-200 122-123° C., ¹H-NMR(CDCl₃)δ1.36(3H, t, J=7.3),2.39(3H, s), 2.40(3H, s), 4.54(2H, q, J=7.3), 5.11(2H, s), 5.69(1H, s),6.76(1H, dd, J=1.8, 8.5), 6.89(1H, d, J=1.8), 7.00(1H, d, J=8.5),7.22-7.50(3H, m), 8.42-8.48(2H, m) Ia-201 147-148° C.,¹H-NMR(CDCl₃)δ1.36(3H, t, J=6.7), 2.39(3H, s), 2.42(3H, s), 3.10(3H, s),4.54(2H, q, J=6.7), 5.13(2H, s), 7.14(1H, d, J=8.5), 7.18-7.28(3H, m),7.31(1H, d, J=1.8), 7.36(2H, d, J=8.5), 7.46-7.50(3H, m), 8.43-8.48(2H,m) Ia-202 99-100° C., ¹H-NMR(CDCl₃)δ1.36(3H, s), 1.77(3H, s), 1.83(3H,s), 2.39(3H, s), 4.54(2H, q, J=7.3), 4.62(2H, d, J=6.7), 5.53(1H, br t,J=6.7), 5.72(1H, s), 6.75(1H, dd, J=2.4, 8.5), 6.87(1H, d, J=2.4),6.93(1H, d, J=8.5), 7.42-7.52(3H, m), 8.42-8.50(2H, m) Ia-203 128-129°C., ¹H-NMR(CDCl₃)δ1.37(3H, t, J=6.7), 1.77(3H, s), 1.82(3H, s), 2.42(3H,s), 3.22(3H, s), 5.34(2H, q, J=6.7), 4.63(2H, d, J=6.7), 5.51(1H, br t,J=6.7), 7.06(1H, d, J=8.5), 7.20(1H, dd, J=2.4, 8.5), 7.30(1H, d,J=1.8), 7.45-7.49(3H, m), 8.43-8.48(2H, m) Ia-206 oil,¹H-NMR(CDCl₃)δ1.33(6H, d, J=6.1), 2.38(3H, s), 5.16(2H, s), 5.55(1H,sept, J=6.1), 5.68(1H, s), 6.75(1H, dd, J=1.8, 8.5), 6.89(1H, d, J=1.8),6.99(1H, d, J=8.5), 7.36-7.48(8H, m), 8.42-8.47(2H, m)

 

TABLE 97 Ia-207 123-124° C., ¹H-NMR(CDCl₃)δ1.33(3H, s), 1.36(3H, s),2.41(3H, s), 3.11(3H, s), 5.18(2H, s), 5.55(1H, sept, J=6.1), 7.13(1H,d, J=8.5), 7.20 (1H, dd, J=1.8, 8.5), 7.31(1H, d, J=1.8), 7.37-7.50(8H,m), 8.42-8.46(2H, m) Ia-208 157-158° C., ¹H-NMR(CDCl₃)δ1.32(3H, s),1.34(3H, s), 2.38(3H, s), 2.40(3H, s), 5.11(2H, s), 5.55(1H, sept,J=6.1), 5.68(1H, s), 6.75(1H, dd, J=2.4, 8.5), 6.88(1H, d, J=2.4),6.99(1H, d, J=8.5), 7.24(1H, d, J=7.9), 7.36(2H, d, J=7.9),7.45-7.52(3H, m), 8.42-8.47(2H, m) Ia-209 159-160° C.,¹H-NMR(CDCl₃)δ1.33(3H, s), 1.35(3H, s), 2.39(3H, s), 2.41(3H, s),3.10(3H, s), 5.13(2H, s), 5.55(1H, sept, J=6.1), 7.13(1H, d, J=7.9),7.18(1H, d, J=1.8), 7.23(1H, d, J=7.3), 7.30(1H, d, J=1.8), 7.36(2H, d,J=7.9), 7.44-7.49(3H, m), 8.42-8.46(2H, m) Ia-210 113-114° C.,¹H-NMR(CDCl₃)δ1.32(3H, s), 1.34(3H, s), 1.77(3H, s), 1.83(3H, s),2.38(3H, s), 4.62(2H, d, J=7.3), 5.49-5.59(2H, m), 5.70(1H, s), 6.73(1H,dd, J=2.4, 8.5), 6.86(1H, d, J=2.4), 6.92(1H, d, J=8.5), 7.45-7.50(3H,m), 8.42-8.46(2H, m) Ia-211 128-129° C., ¹H-NMR(CDCl₃)δ1.33(3H, s),1.35(3H, s), 1.77(3H, s), 1.82(3H, s), 2.41(3H, s), 3.22(3H, s),4.64(2H, d, J=6.7), 5.49-5.60(2H, m), 7.05(1H, d, J=8.5), 7.18(1H, dd,J=1.8, 8.5), 7.29(1H, d, J=2.4), 7.45-7.49(3H, m), 8.42-8.46(2H, m)Ia-214 110-111° C., ¹H-NMR(CDCl₃)δ1.24(3H, t, J=7.6), 2.65(2H, q,J=7.6), 4.02(3H, s), 5.16(2H, s), 5.71(1H, s), 6.74(1H, dd, J=2.0, 8.3),6.88(1H, d, J=2.0), 7.01(1H, d, J=8.3), 7.41-7.49(8H, m), 8.48-8.53(2H,m) Ia-215 161-162° C., ¹H-NMR(CDCl₃)δ1.25(3H, t, J=7.6), 2.66(2H, q,J=7.6), 3.11(3H, s), 4.02(3H, s), 5.17(2H, s), 7.14(1H, d, J=8.5),7.18(1H, dd, J=2.0, 8.5), 7.28(1H, d, J=2.0), 7.37-7.49(8H, m),8.49-8.53(2H, m) Ia-216 121-122° C., ¹H-NMR(CDCl₃)δ1.24(3H, t, J=7.6),2.40(3H, s), 2.65(2H, q, J=7.6), 4.02(3H, s), 5.11(2H, s), 5.70(1H, s),6.74(1H, dd, J=2.0, 8.3), 6.87(1H, d, J=2.0), 7.01(1H, d, J=8.3),7.24(2H, d, J=8.1), 7.34(2H, d, J=8.1), 7.46-7.50(3H, m), 8.49-8.53(2H,m) Ia-217 184-185° C., ¹H-NMR(CDCl₃)δ1.25(3H, t, J=7.6), 2.39(3H, s),2.66(2H, q, J=7.6), 3.10(3H, s), 4.02(3H, s), 5.13(2H, s), 7.14(1H, d,J=8.6), 7.18(1H, dd, J=2.0, 8.6), 7.22(2H, d, J=7.8), 7.27(1H, d,J=2.0), 7.36(2H, d, J=7.8), 7.47-7.51(3H, m), 8.49-8.53(2H, m) Ia-218119-120° C., ¹H-NMR(CDCl₃)δ1.24(3H, t, J=7.6), 1.77(3H, s), 1.83(3H, s),2.65(2H, q, J=7.6), 4.02(3H, s), 4.62(2H, d, J=6.8), 5.51(1H, br t,J=6.8), 5.73(1H, s), 6.73(1H, dd, J=2.0, 8.3), 6.85(1H, d, J=2.0),6.94(1H, d, J=8.3), 7.46-7.50(3H, m), 8.49-8.53(2H, m) Ia-219 141-142°C., ¹H-NMR(CDCl₃)δ1.25(3H, t, J=7.6), 1.77(3H, s), 1.82(3H, s), 2.66(2H,q, J=7.6), 3.22(3H, s), 4.02(3H, s), 4.63(2H, d, J=6.6), 5.51(1H, br t,J=6.6), 7.07(1H, d, J=8.5), 7.17(1H, dd, J=2.0, 8.5), 7.26(1H, d,J=2.0), 7.46-7.50(3H, m), 8.49-8.53(2H, m) Ia-222 187-189° C.,¹H-NMR(CDCl₃)δ5.18(2H, s), 5.76(1H, s), 6.93(1H, dd, J=2.2, 8.3),7.04(1H, d, J=8.6), 7.05(1H, d, J=2.2), 7.42-7.58(8H, m), 8.45-8.49(2H,m), 8.97(1H, s) Ia-223 163-166° C., ¹H-NMR(CDCl₃)δ3.13(3H, s), 5.21(2H,s), 7.19(1H, d, J=8.5), 7.36(1H, dd, J=2.0, 8.5), 7.38-7.54(9H, m),8.45-8.49(2H, m), 8.99(2H, s)

 

TABLE 98 Ia-224 165-166° C., ¹H-NMR(CDCl₃)δ1.78(3H, s), 1.83(3H, s),4.65(2H, d, J=6.8), 5.53(1H, t, J=6.8), 5.77(1H, s), 6.92(1H, dd, J=2.0,8.3), 6.97(1H, d, J=8.3), 7.02(1H, d, J=2.0), 7.54-7.58(3H, m),8.45-8.48(2H, m), 8.97(1H, s) Ia-226 118-119° C., ¹H-NMR(CDCl₃)δ3.87(3H,s), 5.17(2H, s), 5.79(1H, s), 6.88(1H, dd, J=2.2, 8.3), 7.01(1H, d,J=8.3), 7.03(1H, d, J=2.2), 7.39-7.52(8H, m), 8.48-8.51(2H, m), 8.90(1H,s) Ia-227 117-118° C., ¹H-NMR(CDCl₃)δ3.13(3H, s), 3.90(3H, s), 5.19(2H,s), 5.79(1H, s), 7.18(1H, d, J=8.6), 7.33(1H, dd, J=2.2, 8.3), 7.40(1H,d, J=2.2), 7.41-7.53(8H, m), 8.48-8.52(2H, m), 8.90(1H, s) Ia-229 92-94°C., ¹H-NMR(CDCl₃)δ1.77(3H, s), 1.83(3H, s), 3.87(3H, s), 4.63(2H, d,J=6.8), 5.51(1H, t, J=6.8), 5.78(1H, s), 6.88(1H, dd, J=2.0, 8.3),6.95(1H, d, J=8.3), 7.00(1H, d, J=2.0), 7.49-7.51(3H, m), 8.47-8.51(2H,m), 8.90(1H, s) Ia-230 134-135° C., ¹H-NMR(CDCl₃)δ1.77(3H, s), 1.82(3H,s), 3.23(3H, s), 3.91(3H, s), 4.65(2H, d, J=6.6), 5.49(1H, t, J=6.6),7.11(1H, d, J=8.3), 7.32(1H, dd, J=2.0, 8.3), 7.37(1H, d, J=2.0),7.49-7.54(3H, m), 8.48-8.52(2H, m), 8.90(1H, s) Ia-232 151-152° C.,¹H-NMR(CDCl₃)δ2.14(3H, s), 3.13(3H, s), 5.21(2H, s), 7.19(1H, d, J=8.5),7.28(1H, dd, J=2.2, 8.5), 7.38-7.52(9H, m), 8.46-8.49(2H, m), 8.70(2H,s) Ia-233 197-198° C., ¹H-NMR(CDCl₃)δ2.32(3H, s), 2.60(3H, s), 3.11(3H,s), 5.19(2H, s), 7.18(2H, br s), 7.28(1H, m), 7.38-7.50(8H, s),8.49-8.53(2H, m) Ia-235 184-185° C., ¹H-NMR(CDCl₃)δ2.23(3H, s), 3.04(3H,d, J=4.6), 4.55(1H, br q, J=4.6), 5.17(2H, s), 5.82(1H, s), 6.71(1H, dd,J=2.0, 8.1), 6.85(1H, d, J=2.0), 7.04(1H, d, J=8.1), 7.39-7.48(8H, m),8.44-8.48(2H, m) Ia-236 204-205° C., ¹H-NMR(CDCl₃)δ2.23(3H, s), 3.05(3H,d, J=4.6), 3.13(3H, s), 4.51(1H, br q, J=4.6), 5.19(2H, s), 7.16(1H, dd,J=2.0, 8.6), 7.19(1H, d, J=8.6), 7.25(1H, d, J=2.0), 7.38-7.50(8H, m),8.44-8.48(2H, m) Ia-238 oil, ¹H-NMR(CDCl₃)δ1.77(3H, s), 1.82(3H, s),2.35(3H, s), 3.99(3H, s), 4.66(2H, d, J=6.7), 4.78(1H, s), 5.51(1H, brt, J=6.7), 5.69(1H, s), 6.91(2H, d, J=8.6), 6.95(1H, d, J=8.6), 8.01(1H,dd, J=8.6, 1.8), 8.07(1H, d, J=1.8) Ia-239 189-190° C.¹H-NMR(CDCl₃)δ2.34(3H, s), 3.21(3H, s), 3.99(3H, s), 5.20(2H, s),5.70(1H, s), 7.02(1H, d, J=8.6), 7.31-7.47(9H, m), 8.03(1H, dd, J=8.6,1.8), 8.10(1H, d, J=1.8) Ia-240 190-192° C., ¹H-NMR(CDCl₃)δ2.34(3H, s),3.12(3H, s), 3.21(3H, s), 4.00(3H, s), 5.21(2H, s), 7.14(1H, d, J=8.6),7.28-7.49(9H, m), 8.41(1H, dd, J=8.6, 2.5), 8.44(1H, d, J=2.5) Ia-24172-74° C., ¹H-NMR(CDCl₃)δ1.78(3H, s), 1.81(3H, s), 2.34(3H, s), 3.21(3H,s), 3.24(3H, s), 4.01(3H, s), 4.67(2H, d, J=6.7), 5.50(1H, br t, J=6.7),7.08(1H, d, J=8.6), 7.28-7.39(4H, m), 8.39(1H, dd, J=8.5, 1.8), 8.42(1H,s) Ia-248 228-230° C., ¹H-NMR(CDCl₃)δ5.21(2H, s), 7.08(1H, d, J=9.0),7.38-7.56(8H, m), 7.72-7.76(2H, m), 7.85 and 7.88(each 1H, Abq, J=9.0),8.13-8.16(2H, m) Ia-249 220-221° C., ¹H-NMR(CDCl₃)δ3.15(3H, s), 5.23(2H,s), 7.24(1H, d, J=8.8), 7.37-7.58(8H, m), 7.89 and 7.93(each 1H, Abq,J=9.0), 8.07(1H, d, J=2.2), 8.14-8.17(2H, m), 8.21(1H, dd, J=2.2, 8.8)

 

TABLE 99 Ia-252 185-186° C., ¹H-NMR(CDCl₃)δ1.78(3H, s), 1.82(3H, s),4.66(2H, d, J=6.8), 5.52(1H, br t, J=6.8), 5.66(1H, br s), 5.78(1H, s),6.99-7.03(3H, m), 7.68(2H, d, J=9.0), 7.72(1H, dd, J=2.2, 8.6), 7.82(2H,s), 8.06(2H, d, J=8.8) Ia-253 198-200° C., ¹H-NMR(CDCl₃)δ3.15(3H, s),3.21(3H, s), 5.23(2H, s), 7.24(1H, d, J=8.8), 7.38-7.46(5H, m), 7.47(2H,d, J=9.0), 7.91(2H, s), 8.07(1H, d, J=2.2), 8.19(1H, dd, J=2.2, 8.8),8.22(2H, d, J=9.0) Ia-254 192-193° C., ¹H-NMR(CDCl₃)δ1.78(3H, s),1.82(3H, s), 3.21(3H, s), 3.25(3H, s), 4.69(2H, d, J=6.8), 5.51(1H, brt, J=6.8), 7.18(1H, d, J=8.8), 7.48(2H, d, J=9.0), 7.90(2H, s), 8.03(1H,d, J=2.2), 8.22(1H, dd, J=2.2, 8.8), 8.23(2H, d, J=8.8) Ia-255 233-235°C., ¹H-NMR(CDCl₃)δ3.89(3H, s), 5.21(2H, s), 5.75(1H, s), 7.05(2H, d,J=8.8), 7.08(1H, d, J=9.0), 7.37-7.47(5H, m), 7.73-7.75(2H, m), 7.81 and7.83(each 1H, ABq, J=9.3), 8.12(2H, d, J=8.8) Ia-256 212-215° C.,¹H-NMR(CDCl₃)δ3.15(3H, s), 3.89(3H, s), 5.23(2H, s), 7.07(2H, d, J=9.0),7.23(1H, d, J=8.8), 7.37-7.50(5H, m), 7.84 and 7.86(each 1H, ABq,J=9.3), 8.05(1H, d, J=2.0), 8.12(2H, d, J=9.0), 8.18(1H, dd, J=2.0, 8.8)Ia-257 171-174° C., ¹H-NMR(CDCl₃)δ 1.77(3H, s), 1.82(3H, s), 3.89(3H,s), 4.66(2H, d, J=6.8), 5.52(1H, br t, J=6.8), 5.78(1H, s), 7.01(1H, d,J=8.3), 7.05(2H, d, J=8.8), 7.69(1H, d, J=2.2), 7.73(1H, dd, J=2.2,8.3), 7.81 and 7.82 each 1H, ABq, J=9.0), 8.11(2H, d, J=8.8), Ia-258197-199° C., ¹H-NMR(CDCl₃)δ1.78(3H, s), 1.82(3H, s), 3.25(3H, s),3.90(3H, s), 4.68(2H, d, J=6.8), 5.51(1H, br t, J=6.8), 7.06(2H, d,J=9.0), 7.17(1H, d, J=8.8), 7.84 and 7.85(each 1H, ABq, J=9.3), 8.00(1H,d, J=2.2), 8.12(2H, d, J=9.0), 8.20(1H, dd, J=2.2, 8.8) Ia-269 198-199°C., ¹H-NMR(CDCl₃)δ4.83(1H, br s), 5.14(2H, s), 5.69(1H, s), 6.85(2H, d,J=8.8), 6.92(1H, d, J=8.3), 7.09(1H, dd, J=2.2, 8.3), 7.13 and 7.14(each1H, ABq, J=3.9), 7.23(1H, d, J=2.2), 7.38-7.45(5H, m), 7.49(2H, d,J=8.8) Ia-271 167-168° C., ¹H-NMR(CDCl₃)δ1.76(3H, s), 1.81(3H, s),4.60(2H, d, J=6.8), 4.79(1H, s), 5.50(1H, br t, J=6.8), 5.71(1H, s),6.85(2H, d, J=8.8), 6.87(1H, d, J=8.3), 7.09(1H, dd, J=2.2, 8.3), 7.12and 7.14(each 1H, ABq, J=3.7), 7.20(1H, d, J=2.2), 7.50(2H, d, J=8.8)Ia-272 162-164° C., ¹H-NMR(CDCl₃)δ3.12(3H, s), 3.17(3H, s), 5.16(2H, s),7.08(1H, d, J=8.6), 7.21(1H, d, J=3.7), 7.25(1H, d, J=3.7), 7.31(2H, d,J=8.8), 7.39-7.44(5H, m), 7.48(1H, dd, J=2.2, 8.6), 7.57(1H, d, J=2.2),7.64(2H, d, J=8.8) Ia-273 128-129° C., ¹H-NMR(CDCl₃)δ1.76(3H, s),1.80(3H, s), 3.17(3H, s), 3.23(3H, s), 4.62(2H, d, J=6.8), 5.48(1H, brc, J=6.8), 7.02(1H, d, J=8.5), 7.20(1H, d, J=3.9), 7.25(1H, d, J=3.9),7.31(2H, d, J=8.8), 7.48(1H, dd, J=2.2, 8.5), 7.56(1H, d, J=2.2),7.64(2H, d, J=8.8) Ia-275 165-166° C., ¹H-NMR(CDCl₃)δ5.14(4H, s),5.69(2H, s), 6.92(2H, d, J=8.3), 7.09(2H, dd, J=2.2, 8.3), 7.14(2H, s),7.22(2H, d, J=2.2), 7.37-7.44(10H, m) Ia-280 178-179° C.,¹H-NMR(CDCl₃)δ2.31(3H, s), 3.11(3H, s), 4.82(1H, s), 5.16(2H, s),6.84(2H, d, J=8.8), 7.01(1H, s), 7.10(1H, d, J=8.6), 7.34-7.48(9H, m)

 

TABLE 100 Ia-281 128-129° C., ¹H-NMR(CDCl₃)δ1.76(3H, s), 1.82(3H, s),2.31(3H, s), 4.61(2H, d, J=6.8), 4.81(1H, s), 5.51(1H, br t, J=6.8),5.72(1H, s), 6.83(2H, d, J=8.8), 6.90(1H, d, J=8.3), 6.96(1H, dd, J=2.2,8.3), 7.00(1H, s), 7.08(1H, d, J=2.2), 7.47(2H, d, J=8.8) Ia-282133-134° C., ¹H-NMR(CDCl₃)δ2.33(3H, s), 3.12(3H, s), 3.17(3H, s),5.17(2H, s), 7.11(1H, d, J=8.6), 7.12(1H, s), 7.30(2H, d, J=8.8),7.35-7.48(7H, m), 7.61(2H, d, J=8.8) Ia-283 86-87° C.,¹H-NMR(CDCl₃)δ1.76(3H, s), 1.81(3H, s), 2.33(3H, s), 3.17(3H, s),3.22(3H, s), 4.63(2H, d, J=6.8), 5.49(1H, br t, J=6.8), 7.05(1H, d,J=8.6), 7.11(1H, s), 7.29(2H, d, J=8.6), 7.36(1H, dd, J=2.2, 8.6),7.44(1H, d, J=2.2), 7.61(2H, d, J=8.8) Ia-309 128-129° C.,¹H-NMR(CDCl₃)δ2.31(3H, s), 3.64(3H, s), 5.15(2H, s), 5.70(1H, s),6.92(1H, dd, J=2.0, 8.3), 6.98(1H, d, J=8.3), 7.07(1H, d, J=2.0),7.28(1H, br t, J=7.6), 7.38-7.47(7H, m), 7.71(2H, br d, J=7.6) Ia-310132-133° C., ¹H-NMR(CDCl₃)δ2.34(3H, s), 3.11(3H, s), 3.65(3H, s),5.16(2H, s), 7.13(1H, d, J=8.5), 7.29-7.48(m 10H), 7.70(2H, br d, J=7.6)Ia-311 148-149° C., ¹H-NMR(CDCl₃)δ2.30(3H, s), 2.39(3H, s), 3.64(3H, s),5.10(2H, s), 5.69(1H, s), 6.92(1H, dd, J=2.0, 8.3), 6.99(1H, d, J=8.3),7.06(1H, d, J=2.0), 7.23(2H, d, J=8.1), 7.30(1H, m), 7.33(2H, d, J=8.1),7.43(2H, br t, J=8.1), 7.68-7.72(2H, m) Ia-312 146-147° C.,¹H-NMR(CDCl₃)δ2.33(3H, s), 2.38(3H, s), 3.11(3H, s), 3.65(3H, s),5.16(2H, s), 7.13(1H, d, J=8.6), 7.22(2H, d, J=8.1), 7.29-7.47(7H, m),7.68-7.72(2H, m) Ia-313 78-79° C., ¹H-NMR(CDCl₃)δ1.77(3H, s), 1.82(3H,s), 2.33(3H, s), 3.22(3H, s), 3.65(3H, s), 4.62(2H, d, J=6.8), 5.50(1H,br t, J=6.8), 7.06(1H, d, J=8.6), 7.29-7.47(5H, m), 7.68-7.72(2H, m)Ia-314 120-121° C., ¹H-NMR(CDCl₃)δ1.77(3H, s), 1.82(3H, s), 2.30(3H, s),3.64(3H, s), 4.61(2H, d, J=6.8), 5.52(1H, br t, J=6.8), 5.72(1H, s),6.91(2H, br s), 7.04(1H, br s), 7.27(1H, br t, J=7.3), 7.43(2H, br t,J=8.3), 7.70-7.73(2H, m) Ia-315 136-137° C., ¹H-NMR(CDCl₃)δ2.31(3H, s),3.62(3H, s), 3.84(3H, s), 5.16(2H, s), 5.71(1H, s), 6.91-7.01(4H, m),7.07(1H, d, J=1.8), 7.37-7.48(5H, m), 7.61(2H, d, J=8.9) Ia-316 120-121°C., ¹H-NMR(CDCl₃)δ2.32(3H, s), 3.11(3H, s), 3.63(3H, s), 3.84(3H, s),5.16(2H, s), 6.96(2H, d, J=8.9), 7.13(1H, d, J=6.8), 7.32-7.49(7H, m),7.59(2H, d, J=8.9) Ia-317 130-131° C., ¹H-NMR(CDCl₃)δ2.30(3H, s),2.39(3H, s), 3.62(3H, s), 3.84(3H, s), 5.10(2H, s), 5.70(1H, s),6.89-7.00(2H, m), 6.96(2H, d, J=9.2), 7.06(1H, d, J=1.8), 7.23(2H, d,J=7.9), 7.34(2H, d, J=7.9), 7.57(2H, d, J=9.2) Ia-318 145-146° C.,¹H-NMR(CDCl₃)δ2.33(3H, s), 2.38(3H, s), 3.10(3H, s), 3.63(3H, s),3.85(3H, s), 5.11(2H, s), 6.97(2H, d, J=8.5), 7.12(1H, d, J=8.5),7.22(2H, d, J=7.9), 7.34(1H, d, J=8.5), 7.35(2H, d, J=7.9), 7.46(1H, d,J=1.8), 7.57(2H, d, J=8.5) Ia-319 113-114° C., ¹H-NMR(CDCl₃)δ1.76(3H,s), 1.82(3H, s), 2.30(3H, s), 3.62(3H, s), 3.84(3H, s), 4.60(2H, d,J=6.7), 5.52(1H, br t, J=6.7), 6.91(2H, d, J=1.2), 6.96(2H, d, J=9.2),7.04(1H, s), 7.58(2H, d, J=9.2)

 

TABLE 101 Ia-320 66-67° C., ¹H-NMR(CDCl₃)δ1.76(3H, s), 1.81(3H, s), 2.32(3H, s), 3.22(3H, s), 3.63(3H, s), 3.85(3H, s), 4.62(2H, d, J= 6.1),5.50(1H, br t, J=6.1), 6.97(2H, d, J=8.5), 7.05(1H, d, J= 8.5), 7.34(1H,dd, J=1.8, 8.5), 7.44(1H, d, J=1.8), 7.57(2H, d, J=8.5) Ia-322 152-153°C., ¹H-NMR(CDCl₃)δ1.76(3H, s), 1.82(3H, s), 2.24 (3H, s), 3.44(1H, br),3.84(3H, s), 4.60(2H, d, J=6.7), 5.51(1H, br t, J=6.7), 6.78-6.94(5H,m), 7.33(2H, d, J=8.5) Ia-323 oil, ¹H-NMR(CDCl₃)δ0.96(3H, t, J=7.3),2.27(3H, s), 3.82(3H, s), 4.06(2H, q, J=7.3), 5.13(2H, s), 6.18(1H, dd,J=1.8, 7.9), 6.91-6.97(4H, m), 7.32-7.45(7H, m) Ia-324 108-109° C.,¹H-NMR(CDCl₃)δ0.97(3H, t, J=7.3), 2.28(3H, s), 3.12(3H, s), 3.85(3H, s),4.07(2H, q, J=7.3), 5.17(2H, s), 6.96 (1H, d, J=6.7), 7.11(1H, d,J=8.5), 7.24-7.49(9H, m) Ia-325 oil, ¹H-NMR(CDCl₃)δ0.99(3H, t, J=7.3),1.76(3H, s), 1.82(3H, s), 2.28.(3H, s), 3.84., (3H, s), 4.07(2H, q,J=7.3), 4.61(2H, br d, J=6.7), 5.51(1H, br t, J=6.7), 5.78(1H, d,J=1.8), 6.82(1H, dd, J=1.8, 8.5), 6.89-6.98(4H, m), 7.36(2H, d, J=8.5)Ia-326 85-86° C., ¹H-NMR(CDCl₃)δ0.99(3H, t, J=7.3), 1.76(3H, s),1.81(3H, s), 2.28(3H, s), 3.22(3H, s), 3.85(3H, s), 4.07(2H, q, J=7.3),4.63(2H, d, J=6.7), 5.50(1H, br t, J=6.7), 6.96(2H, d, J=8.6), 7.04(1H,d, J=8.6), 7.24-7.29(1H, m), 7.33-7.37(3H, m) Ia-328 140-141° C.,¹H-NMR(CDCl₃)δ1.77(314, s), 1.83(3H, s), 2.34 (3H, s), 3.85(3H, s),4.52(2H, d, J=3.1), 4.62(2H, d, J=6.7), 5.52(1H, br t, J=6.7), 5.78(1H,s), 6.84-7.02(5H, m), 7.58(2H, d, J=8.6) Ia-334 136-137° C.,¹H-NMR(CDCl₃)δ2.13(3H, s), 3.80(3H, s), 5.18 (2H, s), 5.85(1h, s),6.83(1H, dd, J=2.0, 8.3), 6.96(1H, d, J= 2.0), 7.04(1H, d, J=8.3),7.32-7.46(8H, m), 7.69-7.73(2H, m) Ia-335 165-165.5° C.,¹H-NMR(CDCl₃)δ2.15(3H, s), 3.13(3H, s), 3.82(3H, s), 5.20(2H, s),7.19(1H, d, J =8.3), 7.27(1H, dd, J= 2.2, 8.3), 7.33(1H, m), 7.35(1H, d,J=2.2), 7.38-7.50(7H, m), 7.67-7.71(2H, m) Ia-336 143-144° C.,¹H-NMR(CDCl₃)δ1.78(3H, s), 1.83(3H, s), 2.14 (3H, s), 3.80(3H, s),4.64(2H, d, J=6.8), 5.53(1H, br t, J=6.8), 5.84(1H, s),, 6.82(1H, dd,J=2.2, 8.3), 6.93(1H, d, J=2.2), 6.97 (1H, d, J=8.3), 7.32(1H, m),7.43(2H, m), 7.69-7.73(2H, m) Ia-337 126.5-127.5° C.,¹H-NMR(CDCl₃)δ1.78(3H, s), 1.83(3H, s), 2.15(3H, s), 3.24(3H, s),3.82(3H, s), 4.66(2H, d, J=6.8), 5.51 (1H, br t, J=6.8), 7.12(1H, d,J=8.5), 7.26(1H, dd, J=2.2, 8.5), 7.32(1H, m), 7.33(1H, d, J=2.2),7.43(2H, m), 7.67-7.71(2H, m) Ia-338 167-168° C. ¹H-NMR(CDCl₃)δ5.17(2H,s), 5.75(1H, s), 6.99 (1H, d, J=8.6), 7.22(1H, dd, J=2.4, 8.6), 7.32(2H,s), 7.33-7.52 (8H, m), 8.06-8.11(2H, m) Ia-339 149-150° C.¹H-NMR(CDCl₃)δ3.13(3H, s), 5.18(2H, s), 7.14 (1H, d, J=8.5),7.37-7.50(8H, m), 7.60(1H, dd, J=1.8, 8.5), 7.68 (1H, d, J=8.07-8.12(2H,m) Ia-340 184-186° C., ¹H-NMR(CDCl₃)δ2.38(3H, s), 5.12(2H, s), 5.77 (1H,s), 6.99(1H, d, J=8.6), 7.19-7.34(7H, m), 7.40-7.52(3H, m),8.05-8.13(2H, m) Ia-341 175-176° C., ¹H-NMR(CDCl₃)δ2.38(3H, s), 3.12(3H,s), 5.14 (2H, s), 7.14(1H, d, J=8.5), 7.22(2H, d, J=7.9), 7.34(2H, d, J=7.9), 7.37(1H, s), 7.47(2H, d, J=1.8), 7.49(1H, d, J=2.4), 7.60 (1H, dd,J=2.4, 8.5), 8.06-8.12(2H, m)

 

TABLE 102 Ia-342 131—132° C., ¹H-NMR(CDCl₃)δ1.77(3H, s), 1.82(3H, s),4.63 (2H, d, J=6.7), 5.50(1H, br t, J=6.7), 5.78(1H, s), 6.92(1H, d,J=8.5), 7.22(1H, dd, J=2.4, 8.5), 7.30-7.32(2H, m), 7.43-7.51 (3H, m),8.07-8.11(2H, m) Ia-343 126-127° C., ¹H-NMR(CDCl₃)δ1.77(3H, s), 1.81(3H,s), 3.25 (3H, s), 4.64(2H, d, J=6.7), 5.49(1H, br t, J=6.7), 7.07(1H, d,J=8.6), 7.37(1H, s), 7.45-7.53(3H, m), 7.60(1H, dd, J=1.8, 8.6),7.66(1H, d, J=2.4), 8.08-8.12(2H, m) Ia-348 150-151° C.,¹H-NMR(CDCl₃)δ3.85(3H, s), 5.16(2H, s), 5.71 (1H, s), 6.98(4H, d,J=8.9), 7.31-7.46(6H, m), 7.82(1H, s), 8.04 (2H, d, J=8.9) Ia-349112-113° C., ¹H-NMR(CDCl₃)δ3.12(3H, s), 3.88(3H, s), 5.16 (2H, s),6.99(2H, d, J=9.2), 7.12(1H, d J=8.8), 7.33-7.48(5H, m), 7.73(1H, ddJ=8.3, 1.8), 7.74(1H, s), 7.87(1H, s), 8.04(2H, d, J=9.2) Ia-350137-138° C., ¹H-NMR(CDCl₃)δ1.75(3H, s), 1.81(3H, s), 3.87 (3H, s),4.60(2H, d, J=6.8), 5.49(1H, t, J=6.8), 5.70(1H, s), 6.91 (1H, d,J=9.2), 6.98(2H, d, J=9.1), 7.32-7.35(2H, m), 7.82(1H, s), 8.04(2H, d,J=9.1) Ia-351 127-128° C., ¹H-NMR(CDCl₃)δ1.75(3H, s), 1.81(3H, s), 3.23(3H, s), 3.87(3H, s), 4.63(2H, d, J=6.8), 5.48(1H, t, J=6.8), 6.98 (2H,d, J=9.1), 7.05(1H, d, J=9.1), 7.71-7.75(2H, m), 7.85(1H, s), 8.04(2H,d, J=9.1) Ia-352 99-100° C., ¹H-NMR(CDCl₃)δ2.58(3H, s), 3.83(3H, s),5.17 (2H, s), 5.71(1H, s), 6.93-7.01(3H, m), 7.23(1H, d, J=1.9), 7.32(1H, d, J=1.9), 7.34-7.44(5H, m), 8.01(2H, d, J=9.1) Ia-353 159-160° C.,¹H-NMR(CDCl₃)δ2.57(3H, s), 3.11(3H, s), 3.86 (3H, s), 5.17(2H, s),6.97(2H, d, J=9.1), 7.13(1H, d, J=8.5), 7.35-7.47(5H, m), 7.65(2H, d,J=9.1)7.99(2H, d, J=9.1) Ia-354 oil, ¹H-NMR(CDCl₃)δ1.76(3H, s), 1.81(3H,s), 2.16(3H, s), 2.57(3H, s), 3.86(3H, s), 4.61(2H, d, J=6.7), 5.50(1H,br t, J= 6.7), 5.71(1H, s), 6.94(2H, d, J=7.3), 6.97(1H, d, J=8.6), 7.23(1H, dd, J=8.6, 1.8), 7.28(1H, d, J=1.8), 8.00(2H, d, J=7.3) Ia-355130-131° C., ¹H-NMR(CDCl₃)δ1.76(3H, s), 1.81(3H, s), 2.57 (3H, s),3.21(3H, s), 3.87(3H, s), 4.63(2H, d, J=6.7), 5.49(1H, t, J=6.7),6.97(2H, d, J=6.7), 7.07(1H, d, J=9.1)7.62-7.67(2H, m), 7.99(2H, d,J=9.1) Ia-356 mp 91.5-92.5° C.; ¹H NMR(CDCl₃)δ1.74(s, 3H), 1.76(s, 3H),1.77(s, 3H), 1.80(s, 3H), 2.34(s, 3H), 2.54(s, 3H), 3.74(d, J= 6.6Hz,2H), 4.63(d, J=6.6Hz, 2H), 5.37(br t, J=6.6Hz, 1H), 5.54 (br t, J=6.6Hz,1H), 6.68(d, J=8.5Hz, 2H), 7.04(t, J=8.5Hz, 1H), 7.19(d, J=8.5Hz, 2H),7.27(br d, J=8.5Hz, 1H), 7.33(dd, J=2.0, 12.0Hz, 1H)7.39(s, 1H) Ia-357mp 136-136.5° C.; ¹H NMR(CDCl₃)δ1.73(s, 3H), 1.76(s, 3H), 1.77(s, 3H),1.82(s, 3H), 2.37(s, 3H), 2.52(s, 3H), 3.74(d, J= 6.6Hz, 2H), 4.64(d,J=6.8Hz, 2H), 5.35(br t, J=6.6Hz, 1H), 5.55 (br t, J=6.8Hz, 1H), 6.68(d,J=8.8Hz, 2H), 7.01-7.12(m, 3H), 7.35(s, 1H), 7.43(d, J=8.8Hz, 2H)

 

TABLE 103 Ib-3 157-158° C., (CDCl₃)δ1.78(3H, s), 1.82(3H, s), 3.56(3H,s), 3.80 (3H, s), 4.62(2H, d, J=6.8), 5.52(1H, t, J=6.8), 5.69(1H, s),5.84 (1H, s), 6.95(4H, d, J=2.4), 7.05(1H, s), 7.76(1H, td, J=7.8, 1.8),7.94(1H, d, J=7.8), 8.75(1H, dd, J=4.9, 2.4) Ib-8 oil,¹H-NMR(CDCl₃)δ1.76(3H, s), 1.79(3H, s), 2.29(3H, s), 2.37 (3H, s),3.89(3H, s), 4.64(2H, d, J=6.7), 5.57(1H, br t, J=6.7), 6.85-6.96(3H,m), 7.16(1H, s), 7.22-7.27(1H, m), 7.33(1H, s), 7.46(1H, d, J=7.9),7.75(1H, dt, J=1.8, 7.9), 8.71(1H, dd, J=4.9, 1.8). Ib-11 112-113° C.,¹H-NMR(CDCl₃)δ1.45(3H, s), 1.73(3H, s), 1.76 (3H, s), 1.81(3H, s),2.67(3H, s), 3.25(3H, s), 3.68(3H, s), 3.85 (3H, s), 4.39(2H, d, J=7.3),4.64(2H, d, J=6.8), 5.27(1H, t, J=7.3), 5.49(1H, t, J=6.8), 7.09(1H, d,J=8.5), 7.33-7.39(2H, m), 7.49(1H, s), 7.60(1H, dd, J=8.5, 2.5),8.16(1H, d, J=8.5), 8.56(1H, d, J=1.8) Ib-12 139-141° C.,¹H-NMR(CDCl₃)δ2.66(3H, s), 3.12(3H, s), 3.64 (3H, s), 3.82(3H, s),3.84(2H, brs), 5.18(2H, s), 7.05(1H, dd, J= 8.5, 3.0), 7.14(1H, d,J=8.5), 7.32-7.48(8H, m), 7.86(1H, d, J= 8.5), 8.21(1H, d, J=3.0) Ib-13oil, ¹H-NMR(CDCl₃)δ1.76(3H, s), 1.79(3H, s), 2.28(3H, s), 2.36 (3H, s),3.73(2H, br s), 3.88(3H, s), 4.63(2H, d, J=6.8), 5.57(1H, br t, J=6.8),6.84-6.95(3H, m), 7.06(1H, dd, J=2.9, 8.3), 7.14(1H, s), 7.25(1H, dd,J=0.5, 8.3), 8.20(1H, dd, J=0.5, 2.9) Ib-15 157-158° C.,¹H-NMR(CDCl₃)δ2.30(3H, s), 2.35(3H, s), 2.99 (6H, s), 3.70(2H, brs),6.79(2H, d, J=8.9), 7.05(1H, dd, J=8.5, 2.4), 7.13(1H, s), 7.24-7.29(4H,m), 8.20(1H, d, J=2.4) Ib-16 164-165° C., ¹H-NMR(CDCl₃)δ1.75(3H, s),1.78(3H, s), 1.81 (3H, s), 3.56(3H, s), 3.77(2H, d, J=6.8), 3.79(3H, s),4.61(2H, d, J=7.3), 5.34(1H, t, J=6.8), 5.53(1H, t, J=7.3), 5.68(1H, s),5.85 (1H, s), 6.92-6.98(4H, m), 7.05(1H, s), 7.77(1H, d, J=9.2), 8.14(1H, d, J=3.1) Ib-17 oil, ¹H-NMR(CDCl₃)δ1.75(6H, s), 1.78(3H, s),1.79(3H, s), 2.29 (3H, s), 2.37(3H, s), 3.76(2H, d, J=6.6), 3.88(3H, s),4.63(2H, d, J=6.8), 5.35(1H, br t, J=6.6), 5.57(1H, br t, J=6.8),6.84-6.98(4H, m), 7.13(1H, s), 7.27(1H, d, J=8.6), 7.31(1H, s), 8.13(1H,d, J= 2.4) Ib-20 116-117° C., ¹H-NMR(CDCl₃)δ1.75(3H, s), 1.78(3H, s),2.30 (3H, s), 2.36(3H, s), 2.99(6H, s), 3.75(2H, d, J=6.8), 5.35(2H, t,J=6.8), 6.90(2H, d, J=8.5), 6.94(1H, dd, J=8.5, 3.1), 7.13(1H, s),7.22-7.29(4H, m), 8.13(1H, d, J=2.4) Ib-21 233-234° C.,¹H-NMR(CDCl₃)δ2.65(3H, s), 3.13(3H, s), 3.69 (3H, s), 3.84(3H, s),5.19(2H, s), 7.15(1H, d, J=8.5), 7.33-7.48 (8H, m), 8.10(1H, brs),8.16(2H, d, J=1.4), 8.88(1H, s) Ib-23 152-153° C.,¹H-NMR(CDCl₃)δ1.75(3H, s), 1.79(3H, s), 2.30 (3H, s), 2.37(3H, s),3.88(3H, s), 4.63(2H, d, J=6.6), 5.56(1H, br t, J=6.6), 6.84-6.96(3H,m), 7.17(1H, s), 7.32(1H, s), 7.53(1H, d, J=8.5), 8.25(1H, dd, J=2.7,8.5), 8.76(1H, d, J=2.7) Ib-25 178-180° C., ¹H-NMR(CDCl₃)δ2.32(3H, s),2.37(3H, s), 3.00 (6H, s), 6.80(2H, d, J=9.1), 7.17(1H, s), 7.25(2H, d,J=8.5), 7.32 (1H, s), 7.53(1H, d, J=8.5), 8.05(1H, brs), 8.24(1H, dd,J=8.5, 2.5), 8.74(1H, d, J=2.5) Ib-35 219-221° C.,¹H-NMR(CDCl₃)δ3.00(6H, s), 3.09(3H, s), 3.84 (3H, s), 3.86(3H, s),6.50(1H, br), 6.80(2H, d, J=9.0), 6.99(1H, s), 7.51(2H, d, J=9.0),7.52(1H, s), 7.71(1H, dd, J=2.7, 8.7), 8.02(1H, d, J=8.7), 8.52(1H, d,J=2.7)

 

TABLE 104 Ib-37 187-190° C., ¹H-NMR(CDCl₃)δ2.32(3H, s), 2.36(3H, s),3.00 (6H, s), 3.10(3H, s), 6.66(1H, brs), 6.80(2H, d, J=9.2), 7.16(1H,s), 7.18-7.32(3H, m), 7.48(1H, d, J=8.5), 7.76(1H, dd, J=8.5, 3.1),8.51(1H, d, J=3.1) Ib-39 169-170° C., ¹H-NMR(CDCl₃)δ2.67(3H, s),3.06(6H, s), 3.13 (3H, s), 3.65(3H, s), 3.83(3H, s), 5.18(2H, s),7.04(1H, dd, J=8.5, 3.0), 7.13(1H, d, J=8.5), 7.32-7.47(8H, m), 7.93(1H,d, J=8.5), 8.25(1H, d, J=3.0) Ib-40 205-206° C., ¹H-NMR(CDCl₃)δ1.73(3H,s), 1.81(3H, s), 3.06 (6H, s), 3.59(3H, s), 3.80(3H, s), 4.61(2H, d,J=6.8), 5.51(1H, t, J=6.8), 5.70(1H, brs), 5.87(1H, brs), 6.92(3H, s),7.04-7.10(2H, m), 7.82(1H, d, J=8.5), 8.24(1H, d, J=1.8) Ib-41 157-158°C., ¹H-NMR(CDCl₃)δ1.74(3H, s), 1.81(3H, s), 2.70 (3H, s), 3.05(6H, s),3.21(3H, s), 3.61(3H, s), 3.81(3H, s), 4.61 (2H, d, J=6.8), 5.51(1H, t,J=6.8), 7.03-7.11(2H, m), 7.33(1H, dd, J=8.5, 2.0), 7.38(1H, d, J=2.0),7.41(1H, s), 7.92(1H, d, J= 8.5), 8.24(1H, d, J=2.0) Ib-44 117-118° C.,¹H-NMR(CDCl₃)δ1.76(3H, s), 1.80(3H, s), 2.29 (3H, s), 2.36(3H, s),3.04(6H, s), 3.89(3H, s), 4.63(2H, d, J=6.8), 5.57(1H, br t, J=6.8),6.86-6.95(3H, m), 7.08(1H, dd, J=2.9, 8.6), 7.14(1H, s), 7.31(1H, s),7.32(1H, d, J=8.6), 8.22(1H, d, J= 2.9) Ib-46 216-218° C.,¹H-NMR(CDCl₃)δ3.64(3H, s), 3.82(3H, s), 5.16 (2H, s), 5.73(1H, s),5.77(1H, s), 6.94(1H, dd, J=8.5, 2.4), 7.07 (1H, s), 7.09(2H, d, J=6.7),7.36-7.47(5H, m), 8.25(1H, d, J=8.5), 8.54(1H, dd, J=8.5, 2.4), 9.54(1H,d, J=2.4) Ib-47 159-160° C., ¹H-NMR(CDCl₃)δ2.63(3H, s), 3.14(3H, s),3.73 (3H, s), 3.86(3H, s), 5.19(2H, s), 7.16(2H, d, J=8.5), 7.29-7.48(6H, m), 7.56(1H, s), 8.35(1H, d J=9.1), 8.54(1H, dd, J=9.1, 2.5),9.54(1H, d, J=2.5) Ib-49 194-195° C., ¹H-NMR(CDCl₃)δ2.35(3H, s),2.41(3H, s), 3.01 (6H, s), 6.80(2H, d, J=9.1), 7.20(1H, s), 7.26(2H, d,J=9.1), 7.37 (1H, s), 7.67(1H, d, J=9.1), 8.53(1H, dd, J=9.1, 2.5),9.53(1H, d, J=2.4) Ib-51 126-127° C., ¹H-NMR(CDCl₃)δ2.25(3H, s),2.32(3H, s), 3.01 (6H, s), 6.80(2H, d, J=8.5), 7.09(1H, s), 7.18(1H, s),7.22-7.29 (2H, m), 7.38(1H, d, J=8.5), 7.66(1H, dd, J=8.0, 2.4),8.76(1H, d, J=2.4) Ib-54 162-163° C., ¹H-NMR(CDCl₃)δ1.76(3H, s),1.82(3H, s), 3.48 (3H, s), 3.76(3H, s), 4.62(2H, d, J=6.8), 5.53(1H, t,J=6.8), 5.72 (1H, s), 5.81(1H, s), 6.47(1H, s), 6.94-6.99(2H, m),7.04(1H, s), 7.37-7.68(4H, m), 7.99(1H, dd, J=6.1, 1.8)8.62(1H, d,J=4.9), 8.89(1H, d, J=1.8), Ib-58 oil, ¹H-NMR(CDCl₃)δ1.76(3H, s),1.80(3H, s), 2.28(3H, s), 2.30 (3H, s), 3.89(3H, s), 4.64(2H, d, J=6.7),5.57(1H, br t, J=6.7), 6.86-6.96(3H, m), 7.13(1H, s), 7.19(1H, s),7.36(1H, dd, J=8.2, 4.9), 7.70(1H, dt, J=1.8, 8.2), 8.60(1H, dd, J=4.9,1.8), 8.65(1H, d, J=1.8) Ib-65 180-181° C., ¹H-NMR(CDCl₃)δ2.28(3H, s),2.31(3H, s), 3.00 (6H, s), 4.45(2H, br s), 6.57(1H, d, J=9.1), 6.80(2H,d, J=9.1), 7.09(1H, s), 7.15(1H, s), 7.25(2H, dd, J=8.0, 2.4), 7.47(1H,dd, J= 8.5, 2.4), 8.10(1H, d, J=2.4) Ib-67 185-188° C.¹H-NMR(CDCl₃)δ2.07(3H, s), 2.21(3H, s), 2.28 (3H, s), 3.00(6H, s),4.41(2H, brs), 6.41(1H, d, J=7.8), 6.80(2H, d, J=9.2), 6.97(1H, s),7.12(1H, s), 7.22-7.29(3H, m)

 

TABLE 105 Ib-69 mp 184-185.5° C.; ¹H NMR(CDCl₃)δ1.75(s, 3H), 1.77(s,3H), 2.29(s, 3H), 2.30(s, 3H), 3.00(s, 6H), 3.90(br t, J=5.6Hz, 2H),4.45(br s, 1H), 5.37(br t, J 5.6Hz, 1H), 6.45(dd, J=0.5, 8.5Hz, 1H),6.80(d, J=8.8Hz, 2H), 7.10(s, 1H), 7.15(s, 1H), 7.27(d, J= 8.8Hz, 2H),7.47(dd, J=2.4, 8.5Hz, 1H), 8.13(dd, J=0.5, 2.4Hz, 1H) Ib-71 118-119°C., ¹H-NMR(CDCl₃)δ1.73(3H, s), 1.76(3H, s), 2.08 (3H, s), 2.20(3H, s),2.28(3H, s), 3.00(6H, s), 3.83(2H, d, J= 6.8), 4.81(1H, brs), 5.35(1H,t, J=6.7), 6.29(1H, d, J=8.5), 6.79(2H, d, J=8.5), 6.97(1H, s), 7.12(1H,s), 7.24-7.29(3H, m) Ib-73 196-197° C., ¹H-NMR(CDCl₃)δ2.25(3H, s),2.27(3H, s), 2.32 (3H, s), 3.02(6H, s), 6.86(2H, d, J=8.5), 7.11(1H, s),7.17(1H, s), 7.28(2H, d, J=8.5), 7.75(1H, dd, J=8.0, 2.4), 8.19(1H,brs), 8.25-8.28(2H, m) Ib-75 169-171° C., ¹H-NMR(CDCl₃)δ2.05(3H, s),2.22(3H, s), 2.27 (3H, s), 2.29(3H, s), 3.01(6H, s), 6.80(2H, d, J=8.5),6.97(1H, s), 7.14(1H, s), 7.28(1H, d, J=8.5), 7.49(1H, d, J=8.5),7.92(1H, brs), 8.05(1H, d, J=8.5) Ib-79 149-152° C.,¹H-NMR(CDCl₃)δ2.07(3H, s), 2.28(3H, s), 2.29 (3H, s), 3.00(6H, s),3.19(3H, s), 6.80(2H, d, J=9.1), 6.94(1H, s), 7.03(1H, d, J=7.15(1H, s),7.24-7.27(2H, m), 7.47(1H, d, J=8.5) Ib-81 164-165° C.,¹H-NMR(CDCl₃)δ2.69(3H, s), 3.12(3H, s), 3.16 (6H, s), 3.59(3H, s),3.77(3H, s), 5.18(2H, s), 6.59(1H, d, J= 8.5), 6.84(1H, s), 7.14(1H, d,J=8.5), 7.32-7.48(7H, m), 7.84 (1H, dd, J=8.5, 2.4), 8.40(1H, d, J=2.4)Ib-82 72-74° C., ¹H-NMR(CDCl₃)δ1.75(3H, s), 1.82(3H, s), 3.16 (6H, s),3.52(3H, s), 3.74(3H, s), 4.62(2H, d, J=6.8), 5.52(1H, t, J=6.8),5.68(1H, s), 5.85(1H, s), 6.45(1H, s), 6.61(1H, d, J=9.1), 6.94(2H, d,J=1.8), 7.05(1H, d, J=1.2), 7.81(1H, dd, J=8.5, 2.4) 8.46(1H, d, J=2.4),Ib-83 132-133° C., ¹H-NMR(CDCl₃)δ1.75(3H, s), 1.81(3H, s), 2.71 (3H, s),3.15(6H, s), 3.25(3H, s), 3.61(3H, s), 3.77(3H, s), 4.62 (2H, d, J=6.8),5.52(1H, t, J=6.8), 6.59(1H, d, J=8.5), 6.83(1H, s), 7.07(1H, d, J=8.5),7.34(1H, dd, J=8.5, 1.8), 7.38(1H, d, J= 1.8), 7.83(1H, dd, J=6.1, 1.2),8.39(1H, d, J=1.2) Ib-90 91-91.5° C., ¹H-NMR(CDCl₃)δ1.79(3H, s),1.82(3H, s), 2.27 (3H, s), 2.31(3H, s), 3.00(6H, s), 4.87(2H, d, J=7.1),5.57(1H, br t, J=7.1), 6.79-6.83(3H, m), 7.10(1H, s), 7.16(1H, s), 7.27(2H, d, J=8.8), 7.59(1H, dd, J=2.4, 8.3), 8.17(1H, dd, J=0.7, 2.4) Ib-99239-241° C., ¹H-NMR(CDCl₃)δ2.28(3H, s), 2.34(3H, s), 3.02 (6H, s),3.30(3H, s), 6.81(2H, d, J=8.8), 7.26(2H, d, J=8.8), 7.95(1H, dd, J=2.2,8.0), 8.15(1H, dd, J=0.7, 8.0), 8.75(1H, dd, J=0.7, 2.2) Ib-101 159-160°C., ¹H-NMR(CDCl₃)δ1.76(3H, s), 1.82(3H, s), 3.50 (3H, s), 3.76(3H, s),4.62(2H, d, J=6.8), 5.53(1H, t, J=6.8), 5.73(1H, s), 5.84(1H, s),6.48(1H, s), 6.91-6.99(2H, m), 7.04 (1H, d, J=1.8), 7.59(2H, d, J=5.5),8.70(2H, d, J=5.5). Ib-105 113-114° C., 2.28(3H, s), 2.29(3H, s),3.91(3H, s), 5.21(2H, s), 6.83(1H, dd, J=2.0, 8.3), 6.90(1H, d, J=2.0),6.95(1H, d, J=8.3), 7.12(1H, s), 7.17(1H, s), 7.30(2H, d, J=6.1),7.31-7.50(5H, m), 8.65(2H, d, J=6.1) Ib-124 157-158° C.,¹H-NMR(CDCl₃)δ1.76(3H, s), 1.82(3H, s), 3.66 (3H, s), 3.80(3H, s),4.05(3H, s), 4.62(2H, d, J=6.8), 5.52(1H, t, J=6.8), 5.72(1H, s),5.78(1H, s), 6.89-6.98(2H, m), 7.03(1H, d, J=1.8)7.09(1H, s), 7.45(1H,d, J=1.2)8.89(1H, d, J=1.2)

 

TABLE 106 Ib-127 99-100° C., ¹H-NMR(CDCl₃)δ2.32(3H, s), 2.40(3H, s),3.03 (6H, s), 4.04(3H, s), 6.79(2H, d, J=8.7), 6.87(1H, s), 7.16(1H, s),7.25(2H, d, J=7.3), 7.34(1H, s), 8.86(1H, d, J=1.2) Ib-145 184-185° C.,¹H-NMR(CDCl₃)δ2.60(3H, s), 3.14(3H, s), 3.71 (3H, s), 3.84(3H, s),5.19(2H, s), 7.16(1H, d, J=7.9), 7.33(7H, m), 7.58(1H, d, J=8.6),7.59(1H, s), 8.24(1H, d, J=9.2) Ib-146 154-155° C.,¹H-NMR(CDCl₃)δ1.76(3H, s), 1.82(3H, s), 3.62 (3H, s), 3.80(3H, s),4.62(2H, d, J=6.8), 5.53(1H, t, J=6.8), 5.69(1H, s), 5.76(1H, s),6.89-7.03(3H, m), 7.12(1H, s), 7.57 (1H, d, J=8.5)8.14(1H, d, J=9.2)Ib-147 195-196° C., ¹H-NMR(CDCl₃)δ1.77(3H, s), 1.81(3H, s), 2.64 (3H,s), 3.26(3H, s), 3.71(3H, s), 3.84(3H, s), 4.64(2H, d, J= 6.8), 5.49(1H,t, J=6.8), 7.10(1H, d, J=8.6), 7.34(1H, dd, J= 8.5, 1.8), 7.39(1H, d,J=1.8)7.59(1H, s), 7.58(1H, d, J=9.2), 8.23(1H, d, J=9.2) Ib-150197-198° C., ¹H-NMR(CDCl₃)δ2.34(3H, s), 2.39(3H, s), 3.01 (6H, s),6.81(2H, d, J=9.1), 7.21(1H, s), 7.26(2H, d, J=8.5), 7.34(1H, s),7.58(2H, d, J=4.2) Ib-154 185-186° C., ¹H-NMR(CDCl₃)δ2.61(3H, s),3.14(3H, s), 3.25 (6H, s), 3.67(3H, s), 3.81(3H, s), 5.19(2H, s),6.85(1H, d, J= 9.7), 7.14(1H, d, J=8.8), 7.33-7.48(7H, m), 7.65(1H, s),8.02 (1H, d, J=9.7) Ib-162 188-189° C., ¹H-NMR(CDCl₃)δ1.76(3H, s),1.82(3H, s), 3.60 (3H, s), 3.79(3H, s), 4.21(3H, s), 4.62(2H, d, J=6.8),5.52(1H, t, J=6.8), 5.69(1H, s), 5.72(1H, s), 6.91-7.07(4H, m), 7.13(1H,s), 8.06(1H, d, J=9.8) Ib-165 152-153° C., ¹H-NMR(CDCl₃)δ2.33(3H, s),2.39(3H, s), 3.01 (6H, s), 4.19(3H, s), 6.80(2H, d, J=9.1), 7.03(1H, d,J=9.1), 7.19(1H, s), 7.26(2H, d, J=7.8), 7.33(1H, s), 7.53(1H, d, J=9.1)Ib-168 oil, ¹H-NMR(CDCl₃)δ1.77(3H, s), 1.82(3H, s), 3.65(3H, s),3.81(3H, s), 4.63(2H, d, J=6.7), 5.53(1H, br t, J=6.7), 5.74(1H, s),5.77(1H, s), 6.92-6.99(3H, m), 7.04(1H, d, J=1.8), 8.53(1H, d, J=1.8),8.69(1H, s), 9.25(1H, s) Ib-169 165-166° C., ¹H-NMR(CDCl₃)δ1.77(3H, s),1.81(3H, s), 2.72 (3H, s), 3.24(3H, s), 3.77(3H, s), 3.84(3H, s),4.64(2H, d, J= 6.8), 5.49(1H, t, J=6.8), 7.10(1H, d, J=8.5), 7.35(1H,dd, J= 8.5, 2.4), 7.41(1H, d, J=2.4), 7.45(1H, s), 8.57(1H, s), 8.69(1H,s), 9.32(1H, s) Ib-188 165-168° C., ¹H-NMR(CDCl₃)δ2.29(3H, s), 2.42(3H,s), 3.00 (6H, s), 4.46(2H, br s), 5.31(1H, s), 6.78(2H, d, J=8.5), 7.11(1H, s), 7.23(2H, d, J=7.38(1H, s), Ib-198 103-104° C.,¹H-NMR(CDCl₃)δ2.28(3H, s), 2.43(3H, s), 2.99 (6H, s), 3.50(2H, br s),3.74(3H, s), 5.76(1H, s), 6.79(2H, d, J= 8.5), 7.09(1H, s), 7.24(2H, d,J=8.5), 7.43(1H, s) Ib-200 oil, ¹H-NMR(CDCl₃)δ1.73(3H, s), 1.76(3H, s),2.29(3H, s), 2.46(3H, s), 2.99(6H, s), 3.16(1H, brs), 3.68(3H, s),3.70(2H, d, J=5.5), 5.37(1H, br t, J=5.5), 5.67(1H, s), 6.79(2H, d,J=9.2), 7.10(1H, s), 7.24(2H, d, J=9.2), 7.44(1H, s) Ib-202 174-177° C.¹H-NMR(CDCl₃)δ2.31(3H, s), 2.43(3H, s), 3.01 (6H, s), 3.12(3H, s),3.93(3H, s), 6.25(1H, br s), 6.37(1H, s), 6.79(2H, d, J=8.5), 7.10(1H,s), 7.25(2H, d, J=8.5), 7.42(1H, s) Ib-203 234-235° C.,¹H-NMR(CDCl₃)δ3.89(3H, s), 3.95(3H, s), 5.17 (2H, s), 5.56(1H, brs),5.74(1H, brs), 6.92(1H, dd, J=8.2, 2.0), 7.05-7.07(2H, m), 7.39-7.53(7H,m), 7.58(1H, s), 7.95(1H, d, J=8.0), 8.11(1H, d, J=8.3),

 

TABLE 107 Ib-204 197-198° C., ¹H-NMR(CDCl₃)δ2.68(3H, s), 3.14(3H, s),3.93 (3H, s), 4.05(3H, s), 5.20(2H, s), 7.16(1H, d, J=7.3), 7.37-7.53(9H, m), 7.96(1H, d, J=7.3), 8.06(1H, s), 8.11(1H, d, J=8.0) Ib-205189-190° C., ¹H-NMR(CDCl₃)δ1.77(3H, s), 1.83(3H, s), 3.89 (3H, s),3.95(3H, s), 4.63(2H, d, J=6.8), 5.53(1H, t, J=6.8), 5.55 (1H, s),5.76(1H, s), 6.89-7.03(3H, m), 7.41(1H, td, J=7.3, 1.2), 7.52(1H, td,J=7.3, 1.2), 7.58(1H, s), 7.95(1H, d, J=7.3), 8.11(1H, d, J=7.3) Ib-206166-167° C., ¹H-NMR(CDCl₃)δ1.77(3H, s), 1.81(3H, s), 2.72 (3H, s),3.25(3H, s), 3.93(3H, s), 4.05(3H, s), 4.65(2H, d, J= 6.8), 5.49(1H, t,J=6.8), 7.10(1H, d, J=8.5), 7.36-7.53(4H, m), 7.96(1H, d, J=7.3),8.05(1H, s), 8.11(1H, d, J=8.5) Ib-207 mp 75-78° C.; ¹HNMR(CDCl₃)δ1.75(s, 3H), 1.76(s, 3H), 1.77 (s, 3H), 1.81(s, 3H), 2.27(s,3H), 2.36(s, 3H), 3.75(d, J=6.6Hz, 2H), 4.63(d, J=6.6Hz, 2H),5.33-5.36(m, 1H), 5.52-5.57(m, 1H), 6.93-7.11(m, 5H), 7.24-7.30(m, 2H),8.12(d, J=2.4Hz, 1H)IR(KBr): 3405, 2970, 2924, 1596, 1570, 1521, 1493,1466, 1386, 1363, 1299, 1282, 1235, 1196, 1126, 1079, 964 cm⁻¹ Ib-208 mp100-102° C.; ¹H NMR(CDCl₃)δ1.76(s, 3H), 1.81(s, 3H), 2.27(s, 3H),2.34(s, 3H), 3.73(br s, 3H), 4.63(d, J=6.6Hz, 2H), 5.53-5.58(m, 1H),7.00-7.11(m, 5H), 7.23-7.29(m, 2H), 8.20(d, J=2.4Hz, 1H)IR(KBr): 3422,3326, 3202, 2973, 2923, 1618, 1563, 1517, 1484, 1383, 1309, 1298, 1267,1256, 1230, 1125, 1000 cm⁻¹ Ib-209 mp 107-108° C.; ¹H NMR(CDCl₃)δ1.77(s,3H), 1.81(s, 3H), 2.31(s, 3H), 2.40(s, 3H), 4.64(d, J=6.6Hz, 2H),5.52-5.58(m, 1H), 7.02-7.11(m, 3H), 7.18(s, 1H), 7.37(s, 1H), 7.66(d, J=8.7Hz, 1H), 8.54(dd, J=2.4, 8.4Hz, 1H), 9.53(d, J=2.1Hz, 1H) IR(KBr):3440, 2969, 1592, 1572, 1517, 1497, 1460, 1346, 1314, 1294, 1264, 1233,1195, 1128, 990 cm⁻¹ Ib-210 Oil; ¹H NMR(CDCl₃)δ1.77(s, 3H), 1.82(s, 3H),2.29(s, 3H), 2.36(s, 3H), 4.56(d, J=6.6Hz, 2H), 5.54(t, J=6.6Hz, 1H),6.97(d, J=8.1Hz, 2H), 7.15(s, 1H), 7.25(m, 1H), 7.28(d, J=8.1Hz, 2H),7.32(s, 1H), 7.45(d, J=7.5Hz, 1H), 7.75(td, J=7.5, 1.8Hz, 1H), 8.71(d,J=5.1Hz, 1H). Ib-211 mp 91-92° C.; ¹H NMR(CDCl₃)δ1.77(s, 3H), 1.81(s,3H), 2.29 (s, 3H), 2.36(s, 3H), 4.64(d, J=6.6Hz, 2H), 5.55(t, J=6.6Hz,1H), 6.98-7.15(m, 4H), 7.25(m, 1H), 7.32(s, 1H), 7.45(m, 1H)7.,75(m,1H), 8.71(m, 1H); IR(KBr)1584, 1566, 1520, 1498, 1469, 1460, 1433, 1422,1385, 1302, 1278, 1267, 1234, 1129, 998 cm⁻¹. Ib-212 mp 120-122° C.; ¹HNMR(CDCl₃)δ1.13-1.25(m, 4H), 1.62- 1.90(m, 4H), 1.77(s, 3H), 1.81(s,3H), 2.03-2.16(m, 2H), 2.27 (s, 3H), 2.36(s, 3H), 3.31(m, 1H), 4.63(d,J=6.6Hz, 2H), 5.55(t, J=6.6Hz, 1H), 6.90-7.13(m, 5H), 7.21-7.32(m, 2H),8.10(m, 1H); IR(KBr)3392, 1591, 1516, 1482, 1298, 1274, 1262, 1231,1136, 1124, 994, 835 cm⁻¹. Ib-213 ¹H NMR(CDCl₃)δ1.77(s, 3H), 1.82(s,3H), 2.16(s, 6H), 2.27(s, 3H), 3.85(s, 3H), 4.63(d, J=6.6Hz, 2H),5.53-5.58(m, 1H), 6.98-7.13(m, 4H), 7.22-7.30(m, 3H), 8.31(t, J=3.0Hz,1H),; IR(neat): 2960, 2918, 1579, 1496, 1294, 1117, 991, 753 cm⁻¹ Ib-214¹H NMR(CDCl₃)δ1.69(s, 3H), 1.74(s, 3H), 1.77(s, 3H), 1.81(s, 3H),2.17(s, 3H), 2.26(s, 3H), 4.56(d, J=6.6Hz, 2H), 4.63(d, J=6.9Hz, 2H),5.34-5.39(m, 1H), 5.53-5.58(m, 1H), 7.97- 7.13(m, 4H), 7.21-7.29(m, 3H),8.30(dd, J=1.5, 4.5Hz, 1H),; IR(neat): 2968, 2914, 1577, 1516, 1495,1267, 1229, 1117, 995, 841, 782 cm⁻¹

 

TABLE 108 Ib-215 mp 134-136° C.; ¹H NMR(CDCl₃)δ1.77(s, 3H); 1.82(s, 3H);1.93(s, 6H); 1.94(s, 6H); 3.78(br s, 2H); 4.64(d, J=6.6Hz, 2H); 5.57(m,1H); 6.73-7.13(m, 5H); 8.24(m, 1H); IR(KBr): 3465, 3333, 3216, 2920,1633, 1512, 1493, 1461, 1296, 1262, 1242, 1209, 1115 cm⁻¹. Ib-216 mp124-126° C.; ¹H NMR(CDCl₃)δ1.76(s, 3H); 1.77(s, 3H); 1.79(s, 3H);1.82(s, 3H); 1.93(s, 6H); 1.95(s, 6H); 3.74(br, 1H); 3.77(d, J=6.3Hz,2H); 4.64(d, J=6.9Hz, 2H); 5.38(m, 1H); 5.57(m, 1H); 6.73-7.10(m, 5H);8.14(d, J=2.7Hz, 1H); IR(KBr): 3272, 2913, 1596, 1509, 1466, 1302, 1261,1240, 1209, 1115 cm⁻¹. Ib-217 mp 103-110° C.; ¹H NMR(CDCl₃)δ1.77(s, 3H);1.82(s, 3H); 1.91(s, 6H); 1.93(s, 6H); 4.64(d, J=6.6Hz, 2H); 5.57(m,1H); 6.74-7.23(m, 5H); 8.28(d, J=2.7Hz, 1H); IR(KBr): 3441, 2921, 1570,1514, 1462, 1298, 1264, 1241, 1210, 1113, 1004 cm⁻¹. Ib-218 mp 109-110°C.; ¹H NMR(CDCl₃)δ1.78(s, 3H), 1.82(s, 3H), 3.77(s, 3H), 3.78(s, 3H),4.87(d, J=7.2Hz, 2H), 5.57(m, 1H), 6.45-6.55(m, 2H), 6.81(d, J=8.7, Hz,1H), 6.83(s, 1H), 6.91(s, 1H), 7.19(t, J=8.1Hz, 1H), 7.83(dd, J=8.7,2.4Hz, 1H), 8.37(d, J=2.4Hz, 1H)IR(KBr): 3425, 3348, 3223, 1634, 1604,1524, 1484, 1463, 1443, 1396, 1359, 1279, 1209, 1053, 1032, 1003, 867,832, 782, 661 cm⁻¹ Ib-219 mp 99-100° C.; ¹H NMR(CDCl₃)δ1.25(d, J=6.3Hz,6H), 1.78(s, 3H), 1.81(s, 3H), 3.63(m, 1H), 3.77(s, 3H), 3.79(s, 3H),4.87(d, J=6.9Hz, 2H), 5.57(m, 1H), 6.33-6.47(m, 2H), 6.81(d, J=8.7Hz,1H), 6.92(s, 2H), 7.20(t, J=8.4Hz, 1H), 7.83(dd, J=8.7, 2.4Hz, 1H),8.36(d, J=2.4Hz, 1H)IR(KBr): 3408, 1627, 1599, 1526, 1502, 1477, 1280,1246, 1210, 1182, 1133, 1121, 1054, 1030, 968, 869, 837, 783, 668 cm⁻¹Ib-220 mp 139-145° C.; ¹H NMR(CDCl₃)δ1.25(d, J=6.6Hz, 6H), 1.79 (s, 3H),1.82(s, 3H), 3.79(s, 3H), 3.80(s, 3H), 4.53(m, 1H), 4.61 (s, 2H),4.88(d, J=6.9Hz, 2H), 5.57(m, 1H), 6.82(d, J=9.0, Hz, 1H), 6.93(s, 1H),6.96(s, 1H), 7.14-7.24(m, 2H), 7.45(m, 1H), 7.84(dd, J=9.0, 2.1Hz, 1H),8.37(d, J=2.1Hz, 1H). IR(KBr): 3377, 3273, 1656, 1605, 1564, 1520, 1484,1465, 1394, 1339, 1282, 1207, 1055, 1033, 1008, 984, 871, 829, 779, 688,653, 602, 541 cm⁻¹ Ib-221 mp 137-138° C.; ¹H NMR(CDCl₃)δ1.24(d, J=6.9Hz,6H), 1.79 (s, 3H), 1.82(s, 3H), 2.78(d, J=5.4Hz, 3H), 3.79(s, 3H),3.81(s, 3H), 4.17(q, J=5.4Hz, 2H), 4.44(m, 1H), 4.88(d, J=7.2Hz, 2H),5.57(m, 1H), 6.82(d, J=8.7Hz, 1H), 6.93(s, 1H), 6.96(s, 1H),7.12-7.22(m, 2H), 7.44(t, J=8.1Hz, 1H), 7.84(dd, J=8.7, 2.7Hz, 1H),8.38(d, J=2.7Hz, 1H)IR(KBr): 3294, 1604, 1566, 1519, 1484, 1464, 1395,1334, 1281, 1208, 1187, 1153, 1103, 1055, 1035, 1007, 981, 870, 829,779, 688 cm⁻¹ Ib-222 mp 79-80° C.; ¹H NMR(CDCl₃)δ1.73(s, 3H), 1.77(s,3H), 1.78 (s, 3H), 1.81(s, 3H), 3.71(d, J=6.6Hz, 2H), 3.77(s, 3H),3.79(s, 3H), 4.87(d, J=8.4Hz, 2H), 5.35(m, 1H), 5.57(m, 1H), 6.36-6.48(m, 2H), 6.81(d, J=8.4, Hz, 1H), 6.92(s, 2H), 7.21(t, J= 8.4Hz, 1H),7.83(dd, J=8.4, 2.4Hz, 1H), 8.37(d, J=2.4Hz, 1H) IR(KBr): 3416, 1629,1603, 1570, 1526, 1464, 1395, 1278, 1209, 1051, 1034, 1006, 869, 830,777, 666 cm⁻¹

 

TABLE 109 Ib-223 mp 103-104° C.; ¹H NMR(CDCl₃)δ1.56(s, 3H), 1.72(s, 3H),1.78(s, 3H), 1.82(s, 3H), 2.79(d, J=5.1Hz, 3H), 3.78(s, 3H), 3.79(s,3H), 4.22(q, J=5.1Hz, 1H), 4.28(d, J=6.9Hz, 2H), 4.88 (d, J=6.6Hz, 2H),5.30(m, 1H), 5.57(m, 1H), 6.82(d, J=8.1Hz, 1H), 6.91(s, 2H), 6.95(s,1H), 7.17-7.26(m, 2H), 7.37-7.44(m, 1H), 7.83(dd, J=8.1, 2.4Hz, 1H),8.37(d, J=2.4Hz, 1H) IR(KBr): 3404, 3313, 1604, 1566, 1520, 1484, 1465,1395, 1335, 1282, 1209, 1153, 1127, 1055, 1034, 867, 828, 669 cm⁻¹Ib-224 mp 95-96° C.; ¹H NMR(CDCl₃)δ1.70(s, 3H), 1.82(s, 3H), 2.27 (s,3H), 3.82(br, 2H), 4.87(d, J=7.2Hz, 2H), 5.57(m, 1H), 6.64- 6.55(m, 2H),6.81(d, J=8.4, Hz, 1H), 7.50(t, J=8.1Hz, 1H), 7.11 (s, 1H), 7.12(s, 1H),7.59(dd, J=8.4, 2.4Hz, 1H), 8.17(d, J= 2.4Hz, 1H)IR(KBr): 3436, 3328,3218, 1634, 1622, 1606, 1566, 1522, 1480, 1460, 1444, 1396, 1362, 1304,1285, 1245, 1168, 1129, 1008, 834 cm⁻¹ Ib-255 mp 90-91° C.; ¹HNMR(CDCl₃)δ1.26(d, J=6.3Hz, 2H), 1.79(s, 3H), 1.82(s, 3H), 2.22(s, 3H),2.26(s, 3H), 3.64(m, 1H), 4.87(d, J=7.5Hz, 2H), 5.57(m, 1H),6.33-6.47(m, 2H), 6.81(d, J=8.4, Hz, 1H), 7.05(t, J=8.1Hz, 1H), 7.10(s,1H), 7.13(s, 1H), 7.59 (dd, J=8.4, 2.4Hz, 1H), 8.17(d, J=2.4Hz,1H)IR(KBr): 3335, 1628, 1606, 1527, 1481, 1283, 1240, 1183, 1116, 989,835, 812, 635 cm⁻¹ Ib-226 mp 87-88° C.; ¹H NMR(CDCl₃)δ0.91-1.09(m, 2H),1.13-1.36 (m, 4H), 1.40-1.92(m, 5H), 1.79(s, 3H), 1.82(s, 3H), 2.22(s,3H), 2.26(s, 3H), 2.98(d, J=6.6Hz, 2H), 4.87(d, J=7.2Hz, 2H), 5.57(m,1H), 6.32-6.46(m, 2H), 6.80(d, J=8.4Hz, 1H); 7.04(t, J=8.4Hz, 1H),7.10(s, 1H), 7.12(s, 1H), 7.59(dd, J=8.4, 2.4Hz, 1H), 8.17(d, J=2.4Hz,1H)IR(KBr): 3444, 1628, 1603, 1573, 1524, 1481, 1459, 1358, 1278, 1242,1168; 1117, 1006, 974, 825 cm⁻¹. Ib-227 mp 76-77° C.; ¹HNMR(CDCl₃)δ1.55(s, 3H), 1.71(s, 3H), 1.79 (s, 3H), 1.82(s, 3H), 2.19(s,3H), 2.28(s, 3H), 2.80(d, J=5.4Hz, 3H), 4.20(q, J=5.4Hz, 1H), 4.27(d,J=7.2Hz, 2H), 4.87(d, J= 7.2Hz, 2H), 5.29(m, 1H), 5.57(m, 1H), 6.82(d,J=8.1Hz, 1H), 7.13(s, 2H), 7.16-7.31(m, 3H), 7.59(dd, J=8.1, 2.4Hz, 1H),8.17(d, J=2.4Hz, 1H)IR(KBr): 3314, 1605, 1562, 1514, 1481, 1346, 1328,1307, 1283, 1154, 1125, 1072, 1003, 854, 831, 703, 666, cm⁻¹ Ib-228foam; ¹H NMR(CDCl₃)δ1.00-1.74(m, 11H), 1.79(s, 3H), 1.82 (s, 3H),2.13(s, 3H), 2.27(s, 3H), 2.98(d, J=6.6Hz, 2H), 4.87(d, J=6.9Hz, 2H),5.54-5.60(m, 1H), 6.53(dd, J=2.4, 8.1Hz, 1H), 6.68(d, J=2.7Hz, 1H),6.80(d, J=7.8Hz, 1H), 7.01(d, J=8.4Hz, 1H), 7.06(s, 1H), 7.10(s, 1H),7.60(dd, J=2.4, 8.4Hz, 1H), 8.18(d, J=2.1Hz, 1H)IR(KBr): 3413, 2926,2853, 1607, 1517, 1479, 1449, 1376, 1281, 1240, 1033, 977 cm⁻¹. Ib-229mp 110-112° C.; ¹H NMR(CDCl₃)δ1.17-1.79(m, 8H), 1.79(s, 3H), 1.82(s,3H), 2.07-2.14(m, 2H), 2.14(s, 3H), 2.26(s, 3H), 3.23-3.30(m, 1H),3.73(br s, 1H), 4.87(d, J=6.9Hz, 2H), 5.54- 5.60(m, 1H), 6.52(dd, J=2.1,8.1Hz, 1H), 6.68(d, J=2.7Hz, 1H), 6.80(d, J=8.7Hz, 1H), 7.01(d, J=8.4Hz,1H), 7.06(s, 1H); 7.09(s, 1H), 7.60(dd, J=2.7, 8.7Hz, 1H), 8.18(d,J=1.8Hz, 1H)IR(KBr): 3411, 3310, 2926, 2852, 1607, 1517, 1479, 1376,1357, 1302, 1284, 1241, 1013, 980 cm⁻¹

 

TABLE 110 Ib-230 mp oil; ¹H NMR(CDCl₃)δ1.74(s, 3H), 1.78(s, 3H), 1.79(s,3H), 1.82(s, 3H), 2.14(s, 3H), 2.27(s, 3H), 3.71(d, J=6.6Hz, 2H),4.87(d, J=6.9Hz, 2H), 5.33-5.37(m, 1H), 5.55-5.60(m, 1H), 6.55(dd,J=2.4, 8.4Hz, 1H), 6.71(d, J=2.4Hz, 1H), 6.81(d, J= 8.7Hz, 1H), 7.03(d,J=8.1Hz, 1H), 7.06(s, 1H), 7.09(s, 1H), 7.61(dd, J=2.7, 8.7Hz, 1H),8.18(d, J=2.4Hz, 1H)IR(CDCl₃): 3017, 2975, 1607, 1517, 1479, 1378, 1358,1282, 1240, 1227, 1220, 977 cm⁻¹ Ib-231 mp 137-139° C.; ¹HNMR(CDCl₃)δ1.05-1.80(m, 8H), 1.79(s, 3H), 1.82(s, 3H), 2.05-2.12(m, 2H),2.22(s, 3H), 2.26(s, 3H), 3.22-3.30(m, 1H), 3.75(br s, 1H), 4.87(d,J=7.2Hz, 2H), 5.54- 5.60(m, 1H), 6.34-6.44(m, 2H), 6.81(d, J=9.0Hz, 1H),7.03(d, J=8.4Hz, 1H), 7.10(s, 1H), 7.12(s, 1H), 7.59(dd, J=2.4, 8.4Hz,1H), 8.17(d, J=2.7Hz, 1H)IR(KBr): 3331, 2924, 2852, 1628, 1605, 1526,1481, 1452, 1425, 1375, 1334, 1302, 1283, 1241, 1176, 1114, 1016, 986cm⁻¹ Ib-232 mp 108-109° C.; ¹H NMR(CDCl₃)δ1.48-1.78(m, 6H), 1.79(s, 3H),1.82(s, 3H), 2.00-2.09(m, 2H), 2.22(s, 3H), 2.26(s, 3H), 3.75-3.83(m,1H), 3.84-3.90(m, 1H), 4.87(d, J=7.2Hz, 2H), 5.54-5.60(m, 1H),6.35-6.45(m, 2H), 6.80(d, J=8.4Hz, 1H), 7.04(t, J=8.4Hz, 1H), 7.10(s,1H), 7.12(s, 1H), 7.59(dd, J=2.7, 8.4Hz, 1H), 8.17(dd, J=0.6, 2.4Hz,1H)IR(KBr): 3328, 2955, 2866, 1627, 1605, 1526, 1481, 1423, 1394, 1356,1337, 1283, 1240, 1176, 1116, 1016, 974 cm⁻¹ Ib-233 mp 77-79° C.; ¹HNMR(CDCl₃)δ1.00(d, J=0.6Hz, 3H), 1.02(d, J=0.6Hz, 3H), 1.79(s, 3H),1.82(s, 3H), 1.86-1.99(m, 1H), 2.22(s, 3H), 2.26(s, 3H), 2.24(d,J=13.2Hz, 2H), 3.90(br s, 1H), 4.87(d, J=6.6Hz, 2H), 5.54-5.60(m, 1H),6.34-6.50(m, 2H), 6.81(d, J=8.7Hz, 1H), 7.05(t, J=8.4Hz, 1H), 7.10(s,1H), 7.12(s, 1H), 7.59-7.61(m, 1H), 8.16-8.17(m, 1H)IR(KBr): 3340, 2958,2928, 2866, 1627, 1606, 1530, 1481, 1395, 1358, 1337, 1284, 1241, 1178,1115, 1046, 991 cm⁻¹ Ib-234 mp 109-111° C.; ¹H NMR(CDCl₃)δ1.25(t,J=7.2Hz, 3H), 1.78 (s, 3H), 1.82(s, 3H), 2.22(s, 3H), 2.26(s, 3H),2.62-2.70(m, 2H), 4.19(br s, 1H), 4.31(s, 1H), 4.84(d, J=6.6Hz, 2H),5.54- 5.60(m, 1H), 6.39-6.50(m, 2H), 6.81(d, J=9.0Hz, 1H), 7.06(t,J=8.4Hz, 1H), 7.10(s, 1H); 7.12(s, 1H), 7.21(d, J=8.1Hz, 2H), 7.32(d,J=8.1Hz, 2H), 7.59(dd, J=2.7, 8.4Hz, 1H), 8.17(d, J= 1.8Hz, 1H)IR(KBr):3286, 2967, 2927, 2871, 1628, 1598, 1529, 1481, 1469, 1376, 1356, 1336,1274, 1237, 1173, 1149, 1121, 1003, 975 cm⁻¹ Ib-235 mp oil; ¹HNMR(CDCl₃)δ1.26(s, 3H), 1.27(s, 3H), 1.79(s, 3H), 1.82(s, 3H),; 2.22(s,3H), 2.26(s, 3H), 2.87-2.99(m, 1H), 4.31(s, 2H), 4.87(d, J=7.5Hz, 2H),5.55-5.60(m, 1H), 6.40-6.51(m, 2H), 6.81(d, J=8.7Hz, 1H), 7.07(t,J=8.4Hz, 1H), 7.10(s, 1H), 7.12(s, 1H), 7.17(d, J=8.1Hz, 2H), 7.33(d,J=8.1Hz, 2H), 7.57- 7.61(m, 1H), 8.16-8.18(m, 1H)IR(CDCl₃): 3010, 2964,1628, 1603, 1523, 1480, 1357, 1282, 1241, 977 cm⁻¹ Ib-236 mp 203-204°C.; ¹H NMR(CDCl₃)δ1.73(s, 3H), 1.75(s, 3H), 2.19(s, 3H), 2.21(s, 3H),4.39(d, J=4.5Hz, 2H), 4.81(d, J=6.9Hz, 2H), 5.47-5.52(m, 1H),6.48-6.49(m, 1H), 6.62(d, J=8.4Hz, 2H), 6.85(d, J=8.4Hz, 1H),7.05-7.09(m, 4H), 7.50(d, J=8.1Hz, 2H), 7.71(dd, J=2.4, 8.7Hz, 1H),7.92(d, J=8.1Hz, 2H), 8.13(d, J=2.1Hz, 1H)IR(KBr): 3422, 3004, 1686,1609, 1523, 1482, 1423, 1392, 1377, 1356, 1283, 1240, 1182, 1124, 977cm⁻¹

 

TABLE 111 Ib-237 mp 144-147° C.; ¹H NMR(CDCl₃)δ1.79(s, 3H), 1.82(s, 3H),2.26(s, 3H), 2.29(s, 3H), 3.92(s, 3H), 4.46(s, 3H), 4.46(s, 2H), 4.87(d,J=7.2Hz, 2H), 5.54-5.60(m, 1H), 6.65-6.70(m, 2H), 6.76(d, J=8.4Hz, 2H),7.17-7.21(m, 2H), 7.47-7.50(m, 2H), 7.59(dd, J=2.7, 8.4Hz, 2H),8.01-8.05(m, 2H), 8.16(d, J=2.7Hz, 1H)IR(KBr): 3366, 2951, 1709, 1609,1523, 1478, 1469, 1437, 1313, 1282, 1235, 1180, 1115, 1105, 1019, 987cm⁻¹ Ib-238 mp 75-76° C.; ¹H NMR(CDCl₃)δ1.74(s, 3H), 1.77(s, 3H), 1.79(s, 3H), 1.82(s, 3H), 2.06(s, 3H), 2.08(s, 3H), 2.25(s, 3H), 3.72(d,J=6.9Hz, 2H), 4.87(d, J=6.9Hz, 2H), 5.35-5.60(m, 2H), 6.49-6.55(m, 2H),6.79-7.08(m, 4H), 7.60(dd, J=2.7, 8.4Hz, 1H), 8.18(dd, J=0.9, 2.7Hz,1H)IR(KBr): 3331, 2965, 2916, 1610, 1522, 1480, 1449, 1393, 1302, 1283,1251, 1240, 977 cm⁻¹ Ib-239 mp 87-89° C.; ¹H NMR(CDCl₃)δ1.79(s, 3H),1.82(s, 3H), 2.27(m, 3H), 2.30(s, 3H), 3.82(d, J=5.4Hz, 2H), 4.87(d, J=6.9Hz, 2H), 5.18-5.36(m, 2H), 5.54-5.60(m, 1H), 5.93-6.06(m, 1H),6.66-6.71(m, 2H), 6.80(d, J=8.7Hz, 1H), 7.10(s, 1H), 7.15(s, 1H),7.17-7.22(m, 2H), 7.58(dd, J=2.4, 8.4Hz, 1H), 8.16(dd, J=0.6, 2.4Hz,1H)IR(KBr): 3330, 3007, 2973, 2855, 1610, 1526, 1481, 1470, 1392, 1376,1354, 1299, 1283, 1266, 1240, 1129, 1019, 988 cm⁻¹ Ib-240 mp 113-114°C.; ¹H NMR(CDCl₃)δ1.79(s, 3H), 1.82(s, 3H), 2.25-2.27(m, 4H), 2.29(s,3H), 3.99(d, J=2.4Hz, 2H), 4.87(d, J=5.1Hz, 2H), 5.50-5.60(m, 1H),6.73-6.78(m, 2H), 6.81(dd, J=0.6, 8.4Hz, 1H), 7.09(s, 1H), 7.15(s, 1H),7.21-7.25(m, 2H), 7.59(dd, J=2.7, 8.4Hz, 1H), 8.17(dd, J=0.6, 2.4Hz,1H)IR(KBr): 3311, 3271, 2974, 2924, 1609, 1525, 1481, 1392, 1377, 1352,1320, 1300, 1283, 1265, 1239, 1182, 1121, 987 cm⁻¹ Ib-241 mp 125-126°C.; ¹H NMR(CDCl₃)δ0.94-1.87(m, 11H), 1.78(s, 3H), 1.82(s, 3H), 2.26(s,3H), 2.30(s, 3H), 3.00(d, J=6.6Hz, 2H), 4.87(d, J=6.9Hz, 2H),5.54-5.60(m, 1H), 6.60-6.67(m, 2H), 6.81(d, J=8.4Hz, 1H), 7.09(s, 1H),7.15(s, 1H), 7.16- 7.21(m, 2H), 7.58(dd, J=2.4, 8.4Hz, 1H), 8.17(dd,J=0.6, 2.1Hz, 1H)IR(KBr): 3356, 2919, 2851, 1613, 1528, 1482, 1470,1447, 1395, 1355, 1325, 1299, 1284, 1262, 1241, 1182, 1020, 985 cm⁻¹Ib-242 mp 173-175° C.; ¹H NMR(CDCl₃)δ1.14-1.787(m, 8H), 1.78(s, 3H),1.81(s, 3H), 2.08-2.12(m, 2H), 2.27(s, 3H), 2.30(s, 3H), 3.26-3.34(m,1H), 4.87(d, J=7.2Hz, 2H), 5.54-5.60(m, 1H), 6.62-6.67(m, 2H), 6.81(dd,J=0.6, 8.4Hz, 1H), 7.09(s, 1H), 7.15(s, 1H), 7.15-7.19(m, 2H), 7.58(dd,J=2.4, 8.7Hz, 1H), 8.16(dd, J=0.6, 2.4Hz, 1H)IR(KBr): 3326, 2922, 2852,1611, 1523, 1482, 1452, 1393, 1354, 1319, 1300, 1282, 1239, 1182, 1125,983 cm⁻¹ Ib-243 mp 141-142° C.; ¹H NMR(CDCl₃)δ1.78(s, 3H), 1.82(s, 3H),2.26(s, 3H), 2.28(s, 3H), 4.27(br s, 1H), 4.43(br s, 2H), 4.87(d,J=7.2Hz, 2H), 5.54-5.60(m, 1H), 6.63-6.66(m, 2H), 6.81(d, J=8.4Hz, 1H),7.09(s, 1H), 7.13(s, 1H), 7.17-7.20(m, 2H), 7.33-7.35(m, 2H), 7.57(dd,J=2.1, 8.4Hz, 1H), 8.16(d, J= 2.4Hz, 1H), 8.57-8.59(m, 2H)IR(KBr): 3279,2972, 2925, 1603, 1522, 1479, 1459, 1418, 1375, 1351, 1318, 1282, 1272,1240, 1179, 1120, 1001. cm⁻¹

 

TABLE 112 Ib-244 mp 123-125° C.; ¹H NMR(CDCl₃)δ1.78(s, 3H), 1.82(s, 3H),2.26(s, 3H), 2.29(s, 3H), 4.38(s, 2H), 4.87(d, J=6.9Hz, 2H),5.54-5.60(m, 1H), 6.69-6.73(m, 2H), 6.81(dd, J=0.6, 8.4Hz, 1H), 7.09(s,1H), 7.14(s, 1H), 7.17-7.22(m, 2H), 7.26-7.44(m, 5H), 7.58(dd, J=2.4,8.4Hz, 1H), 8.16(d, J=1.8Hz, 1H)IR(KBr): 3348, 2966, 2921, 1613, 1527,1482, 1469, 1453, 1394, 1356, 1326, 1297, 1285, 1264, 1241, 1020, 987cm⁻¹ Ib-245 mp 137-138° C.; ¹H NMR(CDCl₃)δ1.79(s, 3H), 1.82(s, 3H),2.28(s, 6H), 3.33(s, 3H), 4.55(br s, 2H), 4.87(d, J=7.2Hz, 2H),5.54-5.60(m, 1H), 6.81(dd, J=0.6, 8.7Hz, 1H), 7.12-7.14(m, 2H),7.35-7.39(m, 2H), 7.44-7.49(m, 2H), 7.59(dd, J=2.4, 8.4Hz, 1H), 8.17(dd,J=0.6, 2.4Hz, 1H), IR(KBr): 3376, 3284, 2972, 2922, 1604, 1480, 1462,1342, 1281, 1180, 1140, 999 cm⁻¹ Ib-246 mp 118-120° C.; ¹HNMR(CDCl₃)δ1.78(s, 3H), 1.87(s, 3H), 2.26(s, 3H), 2.30(s, 3H), 4.39(s,2H), 4.87(d, J=7.2Hz, 2H), 5.54-5.60(m, 1H), 6.70-6.73(m, 2H), 6.80(d,J=8.4Hz, 1H), 7.10-7.14(m, 3H), 7.15-7.24(m, 3H), 7.34(dd, J=3.0, 5.1Hz,1H), 7.59(dd, J=2.4, 8.4Hz, 1H), 8.17(d, J=1.8Hz, 1H)IR(KBr): 3397,2973, 2920, 2851, 1610, 1522, 1480, 1470, 1376, 1350, 1298, 1280, 1260,1235, 1182, 1122, 980 cm⁻¹ Ib-247 mp 112-115° C.; ¹H NMR(CDCl₃)δ1.79(s,3H), 1.82(s, 3H), 2.27(s, 3H), 2.30(s, 3H), 4.22(s, 2H), 4.87(d,J=6.9Hz, 2H), 5.55-5.60(m, 1H), 6.44-6.45(m, 1H), 6.70-6.74(m, 2H),6.81(dd, J=0.9, 8.4Hz, 1H), 7.09(s, 1H), 7.15(s, 1H), 7.18- 7.23(m, 1H),7.41-7.45(m, 1H), 7.59(dd, J=2.4, 8.7Hz, 1H), 8.17(dd, J=0.6, 2.4Hz,1H), IR(KBr): 3338, 2924, 1613, 1526, 1501, 1482, 1471, 1394, 1355,1317, 1298, 1285, 1241, 1156, 1020, 977 cm⁻¹ Ib-248 mp 123-125° C.; ¹HNMR(CDCl₃)δ1.78(s, 3H), 1.81(s, 3H), 2.27(s, 3H), 2.29(s, 3H), 2.60(brs, 3H), 4.87(d, J=7.2Hz, 2H), 5.54-5.60(m, 1H), 6.73-6.77(m, 2H),6.81(d, J=8.4Hz, 1H), 7.09(s, 1H), 7.14(s, 1H), 7.14-7.18(m, 2H),7.59(dd, J=2.4, 8.4Hz, 1H), 8.17(d, J=2.4Hz, 1H), IR(KBr): 3449, 3341,2972, 2925, 1623, 1604, 1521, 1481, 1394, 1359, 1281, 1241, 1128, 984cm⁻¹ Ib-249 mp 70-72° C.; ¹H NMR(CDCl₃)δ1.79(s, 3H), 1.82(s, 3H), 2.27(s, 3H), 2.30(s, 3H), 2.89(s, 3H), 4.87(d, J=7.2Hz, 2H), 5.55- 5.60(m,1H), 6.66-6.71(m, 2H), 6.81(dd, J=0.9, 8.4Hz, 1H), 7.09(s, 1H), 7.15(s,1H), 7.19-7.23(m, 2H), 7.59(dd, J=2.7, 8.4Hz, 1H), 8.17(dd, J=0.6,2.4Hz, 1H), IR(KBr): 3356, 2923, 2883, 1614, 1603, 1529, 1482, 1393,1357, 1320, 1298, 1282, 1264, 1241, 1182, 981 cm⁻¹ Ib-250 mp 87-88° C.;¹H NMR(CDCl₃)δ1.74(s, 3H), 1.78(s, 3H), 1.79 (s, 3H), 1.80(s, 3H),2.22(s, 3H), 2.26(s, 3H), 3.71(d, J=6.9Hz, 2H), 4.87(d, J=7.2Hz, 2H),5.32-5.37(m, 1H), 5.55-5.60(m, 1H), 6.35-6.47(m, 2H), 6.81(dd, J=0.6,8.4Hz, 1H), 7.02- 7.13(m, 3H), 7.59(dd, J=2.4, 8.4Hz, 1H), 8.16(dd,J=0.9, 5.7Hz, 1H), IR(Nujol): 3330, 2923, 2853, 1627, 1606, 1564, 1527,1481, 1471, 1395, 1376, 1357, 1337, 1284, 1240, 1178, 1116, 990 cm⁻¹

 

TABLE 113 Ib-251 mp 102-103° C.; ¹H NMR(CDCl₃)δ1.75(s, 3H), 1.79(s, 6H),1.82(s, 3H), 2.19(s, 3H), 2.27(s, 3H), 2.31(s, 3H), 3.49(br s, 1H),3.78(d, J=6.9Hz, 2H), 4.87(d, J=6.9Hz, 2H), 5.42(t, J= 6.9Hz, 1H),5.57(t, J=7.2Hz, 1H), 6.68(d, J=8.1Hz, 1H), 6.80(d, J=8.4Hz, 1H),7.09(s, 2H), 7.13-7.17(m, 2H), 7.59(dd, J=2.7, 8.4Hz, 1H), 8.17(d,J=2.4Hz, 1H); IR(KBr): 3363, 2969, 2918, 2884, 2854, 1609, 1601, 1517,1482, 1468, 1442, 1378, 1283, 1250, 981, 891 cm¹. Ib-252 mp 109-110° C.;¹H NMR(CDCl₃)δ1.79(s, 3H), 1.82(s, 3H), 2.23(s, 3H), 2.27(s, 3H),2.30(s, 3H), 3.85(br s, 1H), 4.42(s, 2H), 4.87(d, J=7.2Hz, 2H), 5.57(t,J=6.6Hz, 1H), 6.69(d, J= 8.1Hz, 1H), 7.09-7.15(m, 4H), 7.31-7.44(m, 5H),7.59(dd, J= 2.4, 8.7Hz, 1H), 8.17(d, J=1.5Hz, 1H); IR(KBr): 3431, 3351,2970, 2919, 2854, 1602, 1517, 1483, 1466, 1451, 1377, 1285, 1250, 1132,975, 836 cm⁻¹. Ib-253 mp 72-73° C.; ¹H NMR(CDCl₃)δ1.75(s, 3H), 1.79(s,6H), 1.82 (s, 3H), 2.27(s, 3H), 2.30(s, 3H), 3.77(d, J=6.9Hz, 2H), 3.92(br s, 1H), 4.87(d, J=7.2Hz, 2H), 5.38(t, J=6.9Hz, 1H), 5.57(t, J=6.9Hz,1H), 6.74(dd, J=8.1, 8.7Hz, 1H), 6.81(dd, J=0.9, 6.3Hz, 1H),6.99-7.00(m, 1H), 7.00(s, 1H), 7.03(s, 1H), 7.14(s, 1H), 7.58(dd, J=2.7,8.7Hz, 1H), 8.16(d, J=2.7Hz, 1H); IR(KBr): 3431, 2971, 2915, 1624, 1599,1528, 1479, 1465, 1335, 1241, 1122, 987, 833 cm⁻¹. Ib-254 mp 106-107°C.; ¹H NMR(CDCl₃)δ1.79(s, 3H), 1.82(s, 3H), 2.26(s, 3H), 2.29(s, 3H),4.42(s, 2H), 3.85(br s, 1H), 4.87(d, J= 7.2Hz, 2H), 5.57(t, J=7.2Hz,1H), 6.73(dd, J=8.7, 8.7Hz, 1H), 6.81(d, J=8.4Hz, 1H), 6.96-6.99(m, 1H),7.03(d, J=12.9Hz, 1H), 7.10(d, J=9.9Hz, 2H), 7.26-7.43(m, 5H), 7.58(dd,J=2.4, 8.4Hz, 1H), 8.16(d, J=1.8Hz, 1H); IR(KBr): 3428, 2922, 2857,1623, 1601, 1566, 1500, 1427, 1391, 1376, 1308, 1298, 1149, 1134, 1074,1038, 1018, 927, 895 cm⁻¹. Ib-255 mp 83-84° C.; ¹H NMR(CDCl₃)δ1.75(s,3H), 1.79(s, 6H), 1.82 (s, 3H), 2.27(s, 3H), 2.30(s, 3H), 3.79(d,J=6.3Hz, 2H), 4.29 (br s, 1H), 4.87(d, J=7.2Hz, 2H), 5.39(t, J=6.6Hz,1H), 5.57(t, J=7.2Hz, 1H), 6.71(d, J=8.7Hz, 1H), 6.81(d, J=8.1Hz, 1H),7.10(s, 1H), 7.13(s, 1H), 7.16(dd, J=2.1, 8.4Hz, 1H), 7.27(dd, J=2.1,7.5Hz, 1H), 7.58(dd, J=2.7, 8.7Hz, 1H), 8.16(d, J=1.8Hz, 1H); IR(KBr):3420, 3356, 2968, 2924, 1603, 1520, 1482, 1468, 1284, 1248, 1078, 981,838 cm⁻¹. Ib-256 mp 89-90° C.; ¹H NMR(CDCl₃)δ1.79(s, 3H), 1.82(s, 3H),2.26 (s, 3H), 2.29(s, 3H), 4.46(s, 2H), 4.79(br s, 1H), 4.87(d, J=6.9Hz, 2H), 5.57(t, J=7.2Hz, 1H), 6.69(d, J=8.1Hz, 1H), 6.81(d, J=8.7Hz,1H), 7.09-7.13(m, 3H), 7.31-7.43(m, 6H), 7.58(dd, J=2.7, 8.7Hz, 1H),8.16(d, J=2.4Hz, 1H); IR(KBr): 3422, 3340, 2975, 2923, 1604, 1520, 1482,1455, 1286, 1248, 975, 887 cm⁻¹. Ib-257 mp 62-63° C.; ¹HNMR(CDCl₃)δ1.74(s, 3H), 1.78(s, 3H), 1.79 (s, 3H), 1.82(s, 3H), 2.28(s,3H), 2.32(s, 3H), 3.76(d, J=6.6Hz, 2H), 3.86(s, 3H), 4.27(br s, 1H),4.87(d, J=6.9Hz, 2H), 5.41(t, J=6.6Hz, 1H), 5.58(t, J=6.9Hz, 1H),6.67(d, J=8.1Hz, 1H), 6.78-6.79(m, 2H), 6.88(dd, J=1.8, 8.1Hz, 1H),7.11(s, 1H), 7.18(s, 1H), 7.59(dd, J=2.4, 8.4Hz, 1H), 8.17(d, J=1.8Hz,1H); IR(KBr): 3437, 2880, 2856, 1560, 1416, 1378, 1306, 1176, 1075,1017, 948, 898, 883 cm⁻¹.

 

TABLE 114 Ib-258 mp 86-87° C.; ¹H NMR(CDCl₃)δ1.79(s, 3H), 1.82(s, 3H),2.27(s, 3H), 3.31(s, 3H), 3.87(s, 3H), 4.40(s, 2H), 4.67(br s, 1H),4.87(d, J=6.9Hz, 2H), 5.57(t, J=7.2Hz, 1H), 6.65(d, J= 7.8Hz, 1H),6.79-6.86(m, 3H), 7.10(s, 1H), 7.17(s, 1H), 7.31- 7.44(m, 5H), 7.59(dd,J=2.4, 8.7Hz, 1H), 8.17(d, J=2.4Hz, 1H); IR(KBr): 3426, 2948, 2914,2857, 1600, 1561, 1525, 1415, 1304, 1177, 1018, 948, 900, 883 cm⁻¹.Ib-259 mp 108-109° C.; ¹H NMR(CDCl₃)δ1.74(s, 3H), 1.77(s, 3H), 1.79(s,3H), 1.82(s, 3H), 2.27(s, 3H), 2.31(s, 3H), 3.66(br s, 1H), 3.74(d,J=6.8Hz, 2H), 4.87(d, J=7.1Hz, 2H), 5.38(br t, J= 6.8Hz, 1H), 5.58(br t,J=7.1Hz, 1H), 6.67(d, J=8.5Hz, 2H), 6.81(dd, J=0.7, 8.6Hz, 1H), 7.10(s,1H), 7.15(s, 1H), 7.20(d, J= 8.5Hz, 2H), 7.59(dd, J=2.4, 8.6Hz,1H)8.17(dd, J=0.7, 2.4Hz, 1H) Ib-260 mp 74-75° C.; ¹H NMR(CDCl₃)δ1.72(s,3H), 1.77(s, 3H), 1.81 (s, 6H), 2.29(s, 3H), 2.31(s, 3H), 3.76(d, 2H,J=6.9Hz), 5.07(d, J=7.2Hz, 2H), 5.39(m, 1H), 5.58(m, 1H), 6.77(d,J=7.8Hz, 2H), 7.11-7.23(m, 5H), 8.26(d, J=2.1Hz, 1H), 8.40(d, J=2.1Hz,2H); IR(CHCl₃): 3426, 2975, 2918, 2862, 1612, 1556, 1528, 1498, 1471,1379, 1354, 1299, 1241, 12256, 1185, 1091, 970, 947 cm⁻¹ Ib-261 ¹HNMR(DMSO)δ1.73(s, 3H), 1.76(s, 3H), 2.22(s, 3H), 2.23(s, 3H), 4.82(d,J=6.9Hz, 2H), 5.50(t, J=6.9Hz 1H), 6.86(d, J= 8.4Hz, 1H), 6.96-7.05(m,2H), 7.11-7.17(m, 3H), 7.72(dd, J= 2.7, 8.7Hz, 1H), 8.15(d, J=2.7Hz,1H), 9.94(brs, 1H); IR(neat): 3350, 2964, 1601, 1520, 1480, 1377, 1355,1283, 1241, 1113, 979, 755 cm⁻¹ Ib-262 mp 96° C. ¹H NMR(DMSO)δ1.74(s,6H), 1.76(s, 3H), 1.77(s, 3H), 2.22(s, 3H), 2.34(s, 3H), 4.65(d,J=6.9Hz, 2H), 4.82(d, J= 6.6Hz, 2H), 5.44-5.54(m, 2H), 7.10-7.18(m, 3H),7.21-7.27(m, 2H), 7.73(dd, J=2.4, 8.4Hz, 1H), 8.15(d, J=2.4Hz, 1H),;IR(nujol): 1600, 1517, 1280, 1269, 1127, 995, 836 cm⁻¹ Ib-263 mp 78-79°C. ¹H NMR(CD₃OD)δ1.79(s, 3H), 1.80(s, 3H), 2.42(s, 6H), 3.92(s, 3H),4.83(d, J=7.0Hz, 2H), 5.50-5.56(m, 1H), 6.84(dd, J=0.6, 8.7Hz, 1H),7.05-7.18(m, 5H), 7.67(dd, J=2.7, 8.7Hz, 1H), 8.07(dd, J=2.7, 0.6Hz,1H),; IR(nujol): 1600, 1577, 1280, 1270, 1127, 983, 838 cm⁻¹ Ib-264 mp80-81° C. ¹H NMR(CDCl₃)δ1.79(s, 3H), 1.82(s, 3H), 2.72 (s, 6H), 4.88(d,J=7.2Hz, 2H), 5.13(s, 2H), 5.55-5.60(m, 1H), 6.40(dd, J=1.5, 3.6Hz, 1H),6.48(d, J=3.6Hz, 1H), 6.82(d, J= 8.4Hz, 1H), 7.02-7.06(m, 1H),7.08-7.16(m, 4H), 7.47-7.48(m, 1H), 7.58(dd, J=2.7, 8.4Hz, 1H)8.16(d,J=2.7Hz, 1H); IR(nujol): 1601, 1518, 1281, 1125, 984, 834 cm⁻¹ Ib-265 mp105° C. ¹H NMR(CDCl₃)δ1.79(s, 3H), 1.82(s, 3H), 2.27(s, 6H), 4.88(d,J=7.2Hz, 2H), 5.20(s, 2H), 5.50-5.60(m, 1H), 6.81(d, J=8.4Hz, 1H),7.00-7.15(m, 5H), 7.32-7.50(m, 5H), 7.58(dd, J=2.4, 8.4Hz, 1H)8.16(d,J=2.4Hz, 1H); IR(nujol): 1602, 1299, 1276, 1128, 974, 749 cm⁻¹ Ib-266 mp188-190° C.; ¹H NMR(CDCl₃)δ1.79(s, 3H), 1.82(s, 3H), 2.27(s, 3H),2.29(s, 3H), 4.88(d, J=7.1Hz, 2H), 4.89(s, 2H), 5.58(t, J=7.1Hz, 2H),6.83(dd, J=8.4, 0.6Hz, 1H), 7.13(s, 1H), 7.15(s, 1H), 7.50-7.55(m, 2H),7.59(dd, J=8.4, 2.4Hz, 1H), 7.97-8.02(m, 2H), 8.16(dd, J=2.4, 0.6Hz,1H); IR(KBr): 3367, 3321, 3271, 1602, 1479, 1333, 1281, 1163, 1153, 995,980, 785, 607, 553 cm⁻¹

 

TABLE 115 Ib-267 mp 176-178° C.; ¹H NMR(CDCl₃)δ1.79(s, 3H), 1.82(s, 3H),2.19(s, 3H), 2.28(s, 3H), 488(d, J=6.9Hz, 2H), 4.96(s, 2H), 5.57(t,J=7.1Hz, 2H), 6.82(dd, J=8.4, 0.6Hz, 1H), 7.11(s, 1H), 7.15(s, 1H),7.47(t, J=8.1Hz, 1H), 7.59(dd, J=8.4, 2.6Hz, 1H), 7.74(dd, J=9.0, 1.8Hz,1H), 7.80(dd, J=8.1, 1.8Hz, 1H), 8.16(dd, J=2.6, 0.6Hz, 1H); IR(KBr):3352, 3261, 1603, 1479, 1317, 1152, 993, 831, 777, 600 cm⁻¹ Ib-268 oil;¹H NMR(CDCl₃)δ1.74(s, 3H), 1.78(s, 3H), 1.80(s, 3H), 1.81(s, 3H),2.05(s, 3H), 2.19(s, 3H), 2.26(s, 3H), 3.72(d, J= 6.6Hz, 2H), 3.77(br s,1H), 4.85(m, 2H), 5.35(m, 1H), 5.56(m, 1H), 6.34(dd, J=2.1, 9.3Hz, 1H),6.45(dd, J=2.1, 8.4Hz, 1H), 6.61(d, J=8.4Hz, 1H), 6.97(s, 1H), 7.07(t,J=8.4Hz, 1H), 7.34(d, J=8.4Hz, 1H) Ib-269 oil; ¹H NMR(CDCl₃)δ1.74(s,3H), 1.78(s, 6H), 1.82(s, 3H), 2.21(s, 3H), 2.25(s, 3H), 2.27(s, 3H),3.71(d, J=6.6Hz, 2H), 4.89(d, J=6.6Hz, 2H), 5.35(br t, J=6.6Hz, 1H),5.57(br t, J= 6.6Hz, 1H), 6.39(dd, J=2.1, 12.6Hz, 1H), 6.45(dd, J=2.1,8.4Hz, 1H), 7.06(t, J=8.4Hz, 1H), 7.10(s, 1H), 7.12(s, 1H), 7.41(d, J=2.4Hz, 1H), 8.01(d, J=2.4Hz, 1H) Ib-270 oil; ¹H NMR(CDCl₃)δ1.74(s, 3H),1.78(s, 6H), 1.82(s, 3H), 2.05(s, 3H), 2.07(s, 3H), 2.20(s, 3H), 3.72(d,J=6.6Hz, 2H), 3.85(br, 1H), 4.85(d, J=7.8Hz, 2H), 5.36(m, 1H), 5.56(m,1H), 6.39(dd, J=2.4, 12.3Hz, 1H), 6.45(dd, J=2.4, 8.1Hz, 1H), 6.68(s,1H), 6.97(s, 1H), 7.07(t, J=8.4Hz, 1H), 7.10(s, 1H), 7.93(s, 1H) Ib-271oil, ¹H NMR(CDCl₃)δ1.78(s, 3H), 1.81(s, 3H), 2.20(s, 3H), 2.25(s, 3H),2.27(s, 3H), 4.90(d, J=6.6Hz, 2H), 5.58(br t, J= 6.9Hz, 1H), 6.47(dd,J=2.1, 11.4Hz, 1H), 6.53(dd, J=2.1, 8.1Hz, 1H), 7.05(t, J=8.1Hz, 1H),7.10(s, 1H), 7.11(s, 1H), 7.41(d, J= 2.1Hz, 1H), 8.01(d, J=2.1Hz, 1H)Ib-272 oil; ¹H NMR(CDCl₃)δ1.78(s, 3H), 1.82(s, 3H), 2.05(s, 3H), 2.07(s,3H), 2.19(s, 3H), 3.85(br s, 2H), 4.85(d, J=6.9Hz, 2H), 5.56(m, 1H),6.48(dd, J=2.1, 11.7Hz, 1H), 6.53(dd, J=2.1, 8.4Hz, 1H), 6.68(s, 1H),6.98(s, 1H), 7.07(t, J=8.4Hz, 1H), 7.10(s, 1H), 7.92(s, 1H) Ib-273 oil;¹H NMR(CDCl₃)δ1.74(s, 3H), 1.77(s, 3H), 1.805(s, 3H), 1.810(s, 3H),2.06(s, 3H), 2.26(s, 3H), 2.28(s, 3H), 3.74(d, J= 6.6Hz, 2H),4.83-4.87(m, 2H), 5.38(m, 1H), 5.56(m, 1H), 6.61(d, J=8.4Hz, 1H),6.68(d, J=9.0Hz, 2H), 6.96(s, 1H), 7.21(d, J=9.0Hz, 2H), 7.34(d,J=8.4Hz, 1H) Ib-274 oil; ¹H NMR(CDCl₃)δ1.74(s, 3H), 1.77(s, 3H), 1.78(s,3H), 1.81(s, 3H), 2.25(s, 3H), 2.27(s, 3H), 2.30(s, 3H), 3.74(d, J=6.6Hz, 2H), 4.89(d, J=6.9Hz, 2H), 5.38(m, 1H), 5.58(m, 1H), 6.68(d,J=8.7Hz, 2H), 7.09(s, 1H), 7.15(s, 1H), 7.20(d, J=8.7Hz, 2H), 7.41(m,1H), 8.01(m, 1H) Ib-275 oil; ¹H NMR(CDCl₃)δ1.74(s, 3H), 1.78(s, 6H),1.81(s, 3H), 2.05(s, 3H), 2.07(s, 3H), 2.28(s, 3H), 3.74(d, J=6.9Hz,2H), 4.85(d, J=7.5Hz, 2H), 5.38(m, 1H), 5.56(m, 1H), 6.67-6.71(m, 3H),6.96(s, 1H), 7.12(s, 1H), 7.21(d, J=8.7Hz, 1H), 7.92(s, 1H) Ib-276 oil;¹H NMR(CDCl₃)δ1.75(s, 3H), 1.81(s, 3H), 2.05(s, 3H), 2.06(s, 3H),2.26(s, 3H), 3.75(br, 2H), 4.84-4.87(m, 2H), 5.57(m, 1H), 6.62(d,J=8.1Hz, 1H), 6.74-6.77(m, 3H), 6.96(s, 1H), 7.11(s, 1H), 7.17-7.20(m,2H), 7.34(d, J=8.1Hz, 1H)

 

TABLE 116 Ib-277 oil; ¹H NMR (CDCl₃) δ 1.78(s, 3H), 1.81(s, 3H), 2.25(s,3H), 2.27(s, 3H), 2.28(s, 3H), 4.90(d, J=6.8Hz, 2H), 5.58(m, 1H),6.73-6.78(m, 2H), 7.08-7.41(m, 5H), 8.00(d, J=2.2Hz, 1H) Ib-278 oil; ¹HNMR (CDCl₃) δ 1.78(s, 3H), 1.82(s, 3H), 2.05(s, 3H), 2.08(s, 3H),2.27(s, 3H), 4.85(d, J=8.1Hz, 2H), 5.57(m, 1H), 6.68(s, 1H), 6.75-6.78(m, 2H), 6.97(s, 1H), 7.12(s, 1H), 7.17-7.21(m, 2H), 7.92(s, 1H) Ib-279mp 102-103° C.; ¹H NMR (CDCl₃) δ 1.74(s, 3H), 1.77(s, 3H), 2.26(s, 3H),2.31(s, 3H), 3.74(d, J=6.9Hz, 2H), 4.56-4.60(m, 1H), 4.66-4.73(m, 2H),4.86-4.89(m, 1H), 5.35-5.40(m, 1H), 6.65-6.70(m, 2H), 6.86(d, J=8.4Hz,1H), 7.09(s, 1H), 7.16(s, 1H), 7.18-7.22(m, 2H), 7.62(dd, J=2.4, 8.7Hz,1H), 8.13-8.14(m, 1H) IR (KBr): 3356, 2983, 2925, 1611, 1526, 1482,1452, 1391, 1348, 1307, 1289, 1263, 1242, 1073, 1020 cm⁻¹ Ib-280 mp81-82° C.; ¹H NMR (CDCl₃) δ 2.27(s, 3H), 2.30(s, 3H), 3.82-3.84(m, 2H),4.88-4.91(m, 2H), 5.18-5.47(m, 4H), 5.93-6.21(m, 2H), 6.67-6.71(m, 2H),6.83(d, J=8.4Hz, 1H), 7.09(s, 1H), 7.15(s, 1H), 7.17-7.22(m, 2H),7.61(dd, J=2.4, 7.2Hz, 1H), 8.16(dd, J=0.9, 2.4Hz, 1H) IR (KBr): 3342,3007, 2921, 1609, 1524, 1482, 1391, 1314, 1279, 1182, 1020, 996 cm⁻¹Ib-281 mp 142-144° C.; ¹H NMR (CDCl₃) δ 2.20-2.27(m, 4H), 2.29(s, 3H),2.50(s, 1H), 3.99(d, J=2.4Hz, 1H), 5.04(d, J=2.7Hz, 1H), 6.73-6.78(m,2H), 6.87 (dd, J=2.4, 8.7Hz, 1H), 7.10(s, 1H), 7.16(s, 1H), 7.21-7.26(m,2H), 7.63 (dd, J=2.4, 8.7Hz, 1H), 8.18(dd, J=0.9, 2.4Hz, 1H) IR (KBr):3360, 3292, 3266, 3005, 1608, 1523, 1479, 1438, 1391, 1299, 1280, 1265,1233, 1022, 1010 cm⁻¹ Ib-282 mp 65-68° C.; ¹H NMR (CDCl₃) δ 1.58(s, 3H),1.70(s, 3H), 1.73(s, 3H), 1.78 (s, 3H), 2.23(s, 3H), 2.26(s, 3H),2.43-2.50(m, 2H), 2.87(t, J=7.5Hz, 2H), 3.71(d, J=6.9Hz, 2H), 3.79(br s,1H), 5.20-5.36(m, 2H), 6.36-6.47(m, 2H), 7.06(t, J=8.4Hz, 1H), 7.12(s,1H), 7.14(s, 1H), 7.19(d, J=7.8Hz, 1H), 7.60(dd, J=2.1, 7.8Hz, 1H),8.55(d, J=1.8Hz, 1H) IR (KBr): 3427, 3274, 2965, 2913, 2854, 1629, 1536,1480, 1443, 1421, 1375, 1343, 1305, 1276, 1245, 1173, 1115, 1023 cm⁻¹Ib-283 mp 112-113° C.; ¹H NMR (CDCl₃) δ 1.69(s, 3H), 1.70(s, 3H),1.73(s, 3H), 1.77(s, 3H), 2.22(s, 3H), 2.23(s, 3H), 3.83-3.88(m, 2H),4.64(d, J=7.2Hz, 2H), 5.28-5.33(m, 1H), 5.46-5.51(m, 1H), 6.50-6.61(m,2H), 7.07-7.11(m, 3H), 7.19-7.26(m, 2H), 7.40(dd, J=2.7, 8.7Hz, 1H),7.97(d, J=2.4Hz, 1H), IR (KBr): 3222, 2971, 2922, 2858, 1605, 1536,1493, 1468, 1428, 1396, 1318, 1297, 1272, 1262, 1229, 1194, 1125, 1090,996 cm⁻¹ Ib-284 mp 141-143° C.; ¹H NMR (CDCl₃) δ 1.74(s, 3H), 1.77(s,6H), 1.82(s, 3H), 2.28(s, 3H), 2.29(s, 3H), 3.85-3.95(m, 2H), 4.56(d,J=6.6Hz, 2H), 5.36(m, 1H), 5.54(tm, J=6.6Hz, 1H), 6.45(m, 1H), 6.97(d,J=8.7Hz, 2H), 7.11(s, 1H), 7.14(s, 1H), 7.28(d, J=8.7Hz, 2H), 7.47(m,1H), 8.13(m, 1H); IR (KBr) 3433, 3220, 1610, 1536, 1492, 1233, 1176,998, 844 cm⁻¹. Ib-285 mp 113-114° C.; ¹H NMR (DMSO-d6) δ 1.73(s, 3H),1.77(s, 3H), 2.22(s, 6H), 4.64(d, J=6.9Hz, 2H), 5.46-5.50(m, 1H),5.98(s, 2H), 6.51(d, J= 8.4Hz, 1H), 7.07-7.11(m, 3H), 7.19-7.26(m, 2H),7.41(dd, J=2.7, 8.4Hz, 1H), 7.90(d, J=2.7Hz, 1H), IR (KBr): 3456, 3292,3173, 2917, 1631, 1617, 1521, 1485, 1442, 1395, 1378, 1298, 1268, 1232,1193, 1126, 1004 cm⁻¹

 

TABLE 117 Ib-286 mp 134-136° C.; ¹H NMR (CDCl₃) δ 1.77(s, 3H), 1.82(s,3H), 2.28(s, 6H), 4.56(d, J 6.6Hz, 2H), 5.54(tm, J=6.6Hz, 1H), 6.58(m,1H), 6.98(d, J= 9.0Hz, 2H), 7.10(s, 1H), 7.14(s, 1H), 7.28(d, J=9.0Hz,2H), 7.48(m, 1H), 8.10(m, 1H); IR (KBr) 3458, 3300, 3176, 1630, 1614,1519, 1485, 1238, 1003, 837 cm⁻¹. Ib-287 mp 187-189° C.; ¹H NMR (CDCl₃)δ 1.15-1.54(m, 4H), 1.58-1.86(m, 4H), 1.77(s, 3H), 1.82(s, 3H),2.02-2.15(m, 2H), 2.28(s, 3H), 2.29(s, 3H), 3.58 (m, 1H), 4.56(d,J=6.9Hz, 2H), 5.54(tm, J=6.9Hz, 1H), 5.54(m, 1H), 6.44 (m, 1H), 6.97(d,J=8.7Hz, 2H), 7.10(s, 1H), 7.13(s, 1H), 7.28(d, J= 8.7Hz, 2H), 7.45(m,1H), 8.10(m, 1H); IR (KBr) 3334, 1612, 1519, 1488, 1231, 1006, 833 cm⁻¹.Ib-288 mp 89-90° C.; ¹H NMR (CDCl₃) δ 1.74(s, 3H), 1.78(s, 3H), 2.22(s,3H), 2.26 (s, 3H), 3.71(d, J=6.9Hz, 2H), 5.32-5.36(m, 1H), 5.38(s, 2H),6.36-6.49 (m, 4H), 6.84(dd, J=0.6, 8.4Hz, 1H), 7.06(t, J=8.1Hz, 1H),7.11(s, 1H), 7.13(s, 1H), 7.46-7.48(m, 1H), 7.61(dd, J=2.4, 8.4Hz, 1H),8.18(dd, J= 0.9, 2.4Hz, 1H) IR (KBr): 3423, 2963, 2926, 2860, 1627,1604, 1523, 1480, 1448, 1393, 1378, 1343, 1282, 1269, 1240, 1169, 1150,1117, 1014, 1000 cm⁻¹ Ib-289 mp oil ° C.; ¹H NMR (CDCl₃) δ 1.74(s, 3H),1.77(s, 3H), 1.90(t, J=2.1Hz, 3H), 2.22(s, 3H), 2.26(s, 3H), 3.71(d,J=6.9Hz, 2H), 4.99-5.01(m, 2H), 5.33-5.37(m, 1H), 6.37-6.47(m, 2H),6.86(d, J=8.4Hz, 1H), 7.03-7.13(m, 3H), 7.61(dd, J=2.4, 8.4Hz, 1H),8.17(d, J=2.1Hz, 1H) Ib-290 mp 104-105° C.; ¹H NMR (CDCl₃) δ 1.74(s,3H), 1.78(s, 3H), 2.24(s, 3H), 2.29(s, 3H), 3.72(d, J=6.9Hz, 2H),5.33-5.36(m, 1H), 6.37-6.78(m, 4H), 7.06(t, J=8.4Hz, 1H), 7.14(s, 1H),7.16(s, 1H), 7.38(d, J=8.4Hz, 1H), 7.56(t, J=2.4Hz, 1H), 7.77(dd, J=2.1,8.1Hz, 1H), 8.45(dd, J=0.6, 2.4Hz, 1H) IR (KBr): 3396, 2976, 2929, 2855,1626, 1596, 1573, 1523, 1482, 1378, 1367, 1335, 1130, 1065 cm⁻¹ Ib-291mp 119-120° C.; ¹H NMR (CDCl₃) δ 1.73(s, 3H), 1.77(s, 3H), 2.01-2.06(m,4H), 2.21(s, 3H), 2.29(s, 3H), 3.49-3.54(m, 4H), 3.71(d, J=6.6Hz, 2H),5.33-5.36(m, 1H), 6.35-6.46(m, 3H), 7.06(t, J=8.4Hz, 1H), 7.10(s, 2H),7.48(dd, J=2.7, 9.0Hz, 1H), 8.20(d, J=2.1Hz, 1H) IR (KBr): 3438, 2957,2914, 2855, 1628, 1602, 1540, 1525, 1490, 1457, 1416, 1341, 1306, 1235,1168, 1115 cm⁻¹. Ib-292 Oil; ¹H NMR (CDCl₃) δ 1.78(s, 3H), 1.82(s, 3H),2.27(s, 3H), 2.30(s, 3H), 4.56(d, J=6.9Hz, 2H), 5.55(tm, J=6.9Hz, 1H),6.99(d, J=8.7Hz, 2H), 7.13(s, 1H), 7.17(s, 1H), 7.29(d, J=8.7Hz, 2H),7.37(m, 1H), 7.45(m, H), 8.56-8.70(m, 2H); IR (CHCl₃) 1672, 1607, 1514,1494, 1471, 1450, 1383, 1234, 1230, 1174, 998, 978 cm⁻¹. Ib-293 mp114-115° C.; ¹H NMR (CDCl₃) δ 1.73(s, 3H), 1.77(s, 3H), 2.26(s, 3H),2.31(s, 3H), 3.74(d, J=6.9Hz, 2H), 3.99(s, 3H), 5.35-5.44(m, 1H), 6.65-6.70(m, 2H), 6.81(d, J=8.4Hz, 1H), 7.10(s, 1H), 7.16(s, 1H),7.17-7.22(m, 2H), 7.60(dd, J=2.4, 8.4Hz, 1H), 8.18(d, J=2.1Hz, 1H) IR(KBr): 3333, 3006, 2968, 1612, 1524, 1483, 1387, 1367, 1319, 1300, 1288,1240, 1024 cm⁻¹ Ib-294 mp 75-76° C.; ¹H NMR (CDCl₃) δ 1.73(s, 3H),1.77(s, 3H), 2.28(s, 3H), 2.31 (s, 3H), 3.76(d, J=6.9Hz, 2H), 4.17(s,2H), 5.39(m, 1H), 6.75(d, J=8.4Hz, 2H), 7.10-7.22(m, 4H), 8.29(d,J=2.4Hz, 1H), 8.42(d, J=2.4Hz, 1H); IR (CHCl₃): 3426, 2923, 2868, 1613,1557, 1530, 1499, 1478, 1427, 1381, 1353, 1301, 1245, 1093, 1007, 956,929, 894 cm⁻¹

 

TABLE 118 Ib-295 mp 88-89° C. ¹H NMR (CDCl₃) δ 1.77(s, 3H), 1.82(s, 3H),2.28(s, 6H), 4.64(d, J=6.9Hz, 2H), 5.44(s, 2H), 5.53-5.58(m, 1H),6.89(dd, J=0.6, 8.7Hz, 1H), 7.00-7.14(m, 5H), 7.32-7.44(m, 3H),7.49-7.53(m, 2H), 7.62 (dd, J=2.7, 8.7Hz, 1H) 8.19(dd, J=0.6, 2.7Hz,1H); IR (nujol): 1602, 1285, 1129, 988, 836 cm⁻¹. Ib-296 mp 110° C. ¹HNMR (CDCl₃) δ 1.77(s, 3H), 1.81(s, 3H), 2.27(s, 6H), 2.28 (s, 3H),4.01(s, 3H), 4.64(d, J=6.9Hz, 2H), 5.53-5.58(m, 1H), 6.82(d, J=8.4Hz,1H), 7.00-7.26(m, 5H), 7.60(dd, J=2.4, 8.4Hz, 1H), 8.18(d, J=2.4 Hz,1H),; IR (nujol): 1598, 1283, 1273, 1124, 992, 838 cm⁻¹ Ib-297 mp201-204° C.; ¹H NMR (CDCl₃) δ 1.80(s, 3H), 1.83(s, 3H), 1.97(s, 6H),1.98(s, 6H), 4.88(d, J=6.9Hz, 2H), 5.56-5.61(m, 1H), 6.75-6.80(m, 2H),6.83(d, J=8.1Hz, 1H), 6.92-6.98(m, 2H), 7.41(dd, J=2.4, 8.7Hz, 1H), 7.98(d, J=2.4Hz, 1H) IR (KBr): 3452, 3368, 2927, 1619, 1599, 1517, 1487,1465, 1378, 1350, 1275, 1240, 1125, 980 cm⁻¹ Ib-298 mp 158-160° C.; ¹HNMR (CDCl₃) δ 1.74(s, 3H), 1.78(s, 3H), 1.79(s, 3H), 1.83(s, 3H),1.97(s, 6H), 2.00(s, 6H), 3.74(d, J=6.9Hz, 2H), 4.88(d, J= 6.9Hz, 2H),5.37-5.42(m, 1H), 5.56-5.62(m, 1H), 6.67-6.72(m, 2H), 6.84(d, J=8.4Hz,1H), 6.94-7.00(m, 2H), 7.41(dd, J=2.4, 8.7Hz, 1H), 7.99(dd, J= 0.6,2.4Hz, 1H) IR (KBr): 3388, 2928, 2854, 1613, 1600, 1518, 1486, 1465,1376, 1349, 1312, 1291, 1275, 1240, 1125, 983 cm⁻¹ Ib-299 mp 124-125°C.; ¹H NMR (CDCl₃) δ 1.25(s, 3H), 1.27(s, 3H), 1.80(s, 3H), 1.83(s, 3H),1.97(s, 6H), 2.00(s, 6H), 3.62-3.75(m, 1H), 4.88(d, J=6.9Hz, 2H),5.56-5.62(m, 1H), 6.64-6.68(m, 2H), 6.83(d, J=8.4Hz, 1H), 6.93- 6.98(m,2H), 7.41(dd, J=2.4, 8.4Hz, 2H), 7.99(d, J=1.8Hz, 1H) IR (KBr): 3391,2965, 2930, 1613, 1600, 1519, 1412, 1376, 1362, 1349, 1316, 1277, 1242,1181, 1125, 977 cm⁻¹ Ib-300 mp 116-119° C.; ¹H NMR (CDCl₃) δ 1.78(s,3H); 1.82(s, 3H); 1.97(s, 12H); 4.01(s, 3H); 4.64(d, J=6.6Hz, 2H);5.58(m, 1H); 6.82-6.87(m, 2H); 6.91 (ddd, J=1.8, 4.8, 11.7Hz, 1H);7.05(dt, J=1.5, 8.7Hz, 1H); 7.41(ddd, J= 1.5, 2.4, 8.7Hz, 1H); 7.99(d,J=2.4Hz, 1H); IR (KBr): 3432, 2944, 1603, 1514, 1496, 1462, 1297, 1281,1263, 1245, 1210, 1113 cm⁻¹. Ib-301 mp 150-153° C.; ¹H NMR (CDCl₃) δ1.75(s, 3H); 1.780(s, 3H); 1.784(s, 3H); 1.82(s, 3H); 1.96(s, 6H);2.01(s, 6H); 3.91(t, J=6.0Hz, 2H); 4.50(br t, J= 4.5Hz, 1H); 4.64(d,J=6.9Hz, 2H); 5.38(m, 1H); 5.57(m, 1H); 6.49(m, 1H); 6.84(m, 1H);6.91(ddd, J=2.1, 3.3, 12Hz, 1H); 7.04(dt, J=2.1, 8.4Hz, 1H); 7.27(m,1H); 7.91(m, 1H); IR (KBr): 3235, 2917, 1608, 1540, 1513, 1381, 1294,1261 cm⁻¹. Ib-302 mp 155-157° C.; ¹H NMR (CDCl₃) δ 1.30(d, J=6.3Hz, 6H);1.78(s, 3H); 1.83 (s, 3H); 1.96(s, 6H); 2.01(s, 6H); 3.92(sept, J=6.3Hz,1H); 4.54(br, 1H); 4.64(d, J=6.6Hz, 2H); 5.58(m, 1H); 6.48(d, J=7.5Hz,1H); 6.83-7.07(m, 3H); 7.27(m, 1H); 7.89(m, 1H); IR (KBr): 3419, 3249,2969, 1610, 1537, 1513, 1463, 1389, 1293, 1263, 1241, 1209, 1180, 1113cm⁻¹. Ib-303 mp 134-137° C.; ¹H NMR (CDCl₃) δ 0.99-1.92(m, 11H); 1.77(s,3H); 1.82(s, 3H); 1.96(s, 6H); 2.01(s, 6H); 3.16(t, J=6.0Hz, 2H);4.64(d, J=6.6Hz, 2H); 4.73(br s, 1H); 5.57(m, 1H); 6.49(m, 1H);6.82-6.94(m, 2H); 7.04(dt, J=1.5, 7.8Hz, 1H); 7.27(m, 1H); 7.88(m, 1H);IR (KBr): 3425, 3250, 2925, 2852, 1607, 1533, 1512, 1448, 1294, 1261,1240, 1211, 1115 cm⁻¹.

 

TABLE 119 Ib-304 mp 154-156° C.; ¹H NMR (CDCl₃) δ 1.77(s, 3H); 1.82(s,3H); 1.98(s, 6H); 2.00(s, 6H); 4.63(d, J 5.7Hz, 2H); 5.00(br, 1H);5.57(m, 1H); 6.52(dd, J= 2.4, 8.4Hz, 1H); 6.85-7.01(m, 2H); 7.04(dt,J=1.8, 8.4Hz, 1H); 7.26-7.33 (m, 2H); 7.77(m, 1H); 7.994(m, 1H); 8.56(m,1H); 8.69(br s, 1H); IR (KBr): 3256, 2917, 1603, 1514, 1463, 1427, 1381,1296, 1263, 1239, 1210, 1112, 1004 cm⁻¹. Ib-305 mp 127-129° C.; ¹H NMR(CDCl₃) δ 0.99(d, J=6.6Hz, 6H); 1.50-1.80(m, 3H); 1.77(s, 3H); 1.82(s,3H); 1.96(s, 6H); 2.01(s, 6H); 3.29-3.36(m, 2H); 4.53(br t, 1H); 4.64(d,J=6.6Hz, 2H); 5.57(m, 1H); 6.49(d, J=8.4Hz, 1H); 6.81-6.94(m, 2H);7.04(dt, J=1.5, 8.4Hz, 1H); 7.28(m, 2H); 7.90(m, 1H); IR (KBr): 3442,3259, 2956, 1609, 1542, 1512, 1457, 1383, 1293, 1260, 1238, 1205, 1114cm⁻¹. Ib-306 mp 86-89° C.; ¹H NMR (CDCl₃) δ 1.04(d, J=6.6Hz, 5H);1.77(s, 3H); 1.82(s, 3H); 1.86-1.95(m, 1H); 1.96(s, 6H); 2.01(s, 6H);3.14(t, J=6.3Hz, 2H); 4.64(d, J=6.9Hz, 2H); 4.67(br t, 1H); 5.57(m, 1H);6.49(m, 1H); 6.82-7.07 (m, 3H); 7.28(dt, J=1.8, 8.4Hz, 1H); 7.89(m, 1H);IR (KBr): 3343, 2957, 1610, 1513, 1465, 1382, 1294, 1263, 1240, 1114cm⁻¹. Ib-307 mp 157-159° C.; ¹H NMR (CDCl₃) δ 1.77(s, 3H); 1.82(s, 3H);1.96(s, 6H); 2.00(s, 6H); 4.64(d, J=6.6Hz, 2H); 4.77(d, J=5.4Hz, 2H);4.94(br, 1H); 5.57(m, 1H); 6.56(m, 1H); 6.81-7.09(m, 5H); 7.24-7.30(m,2H); 7.96(d, J= 2.4Hz, 1H); IR (KBr): 3393, 2925, 1610, 1512, 1295,1263, 1240 cm⁻¹. Ib-308 mp 175-177° C.; ¹H NMR (CDCl₃) δ 1.77(s, 3H);1.82(s, 3H); 1.96(s, 6H); 2.00(s, 6H); 4.58(d, J=6.0Hz, 2H); 4.64(d,J=6.9Hz, 2H); 4.98(br s, 1H); 5.57(m, 1H); 6.54(m, 1H); 6.81-6.94(m,2H); 7.04(dt, J=1.8, 8.4Hz, 1H); 7.14(dd, J=1.8, 5.1Hz, 1H); 7.27(m,1H); 7.35(dd, J=3.0, 4.8Hz, 1H); 7.94(m, 1H); IR (KBr): 3233, 2912,1546, 1512, 1453, 1420, 1384, 1317, 1294, 1259, 1238, 1204, 1116 cm⁻¹.Ib-309 mp 134-137° C.; ¹H NMR (CDCl₃) δ 1.77(s, 3H); 1.82(s, 3H);1.98(s, 6H); 2.00(s, 6H); 4.58(d, J=5.4Hz, 2H); 4.64(d, J=6.6Hz, 2H);4.88(br t, 1H); 5.57(m, 1H); 6.30(dd, J=0.9, 3.0Hz, 1H), 6.36(dd, J=4.2,6.3Hz, 1H); 6.57(m, 1H); 6.86(m, 1H); 6.91(ddd, J=2.1, 3.6, 11.7Hz, 1H);7.03(dt, J= 1.8, 8.4Hz, 1H); 7.28(m, 1H); 7.40(m, 1H); 7.94(m, 1H); IR(KBr): 3379, 2928, 1513, 1294, 1263, 1240 cm⁻¹. Ib-310 mp 124-126° C.;¹H NMR (CDCl₃) δ 1.77(s, 3H); 1.82(s, 3H); 1.97(s, 6H); 2.00(s, 6H);4.41(d, J=5.4Hz, 2H); 4.64(d, J=6.3Hz, 2H); 4.73(br t, 1H); 5.57(m, 1H);6.47(m, 1H), 6.54(m, 1H), 6.82-7.08(m, 3H), 7.27(m, 1H), 7.43(t,J=1.8Hz, 1H), 7.46(m, 1H); 7.94(d, J=2.4Hz, 1H); IR (KBr): 3456, 3236,2254, 1605, 1512, 1468, 1382, 1293, 1261, 1240, 1209, 1114 cm⁻¹. Ib-311mp 143-145° C.; ¹H NMR (CDCl₃) δ 1.78(s, 3H); 1.82(s, 3H); 1.97(s, 6H);2.00(s, 6H); 4.64(d, J=7.0Hz, 2H); 4.74(d, J=5.2Hz, 2H); 5.58(m, 1H);5.76(m, 1H), 6.61(d, J=8.4Hz, 1H); 682-7.29(m, 4H); 7.40(d,J=8.0Hz, 1H);7.70(m, 1H); 7.95(d, J=2.0Hz, 1H); 8.61(d, J=4.8Hz, 1H); IR (KBr): 3251,2929, 1608, 1514, 1440, 1380, 1295, 1264, 1252, 1240, 1207 cm⁻¹. Ib-312mp 166-167° C.; ¹H NMR (CDCl₃) δ 1.77(s, 3H); 1.82(s, 3H); 1.96(s, 6H);1.99(s, 6H); 4.5l(br s, 2H); 4.64(d, J=6.6Hz, 2H); 5.57(m, 1H); 6.62(m,1H); 6.84(m, 1H); 6.90(m, 1H); 7.04(m, 1H); 7.27(m, 1H); 7.90(m, 1H); IR(KBr): 3467, 3304, 3168, 2917, 1638, 1619, 1516, 1388, 1297, 1265, 1240,1209 cm⁻¹.

 

TABLE 120 Ib-313 amorphous; ¹H NMR (CDCl₃) δ 1.75(s, 3H), 1.78(s, 3H),1.98(s, 6H), 2.01(s, 6H), 3.69(br s, 1H), 3.91(t, J=5.6Hz, 2H), 4.64(brs, 1H), 5.38(t, J=6.9Hz, 1H), 6.50(d, J=8.7Hz, 1H), 6.75-6.79(m, 2H),6.92-6.97(m, 2H), 7.30(dd, J=8.7, 2.1Hz, 1H), 7.91(d, J=2.1Hz, 1H),7.56(dd, J=9.3, 2.4Hz, 1H); IR (KBr): 3447, 3414, 3364, 1605, 1518,1464, 1377, 1278, 819 cm⁻¹ Ib-314 mp 172-173° C.; ¹H NMR (CDCl₃) δ1.75(s, 6H), 1.78(s, 3H), 1.78(s, 3H), 2.00(s, 6H), 2.01(s, 6H), 3.4(brs, 1H), 3.74(d, J=6.6Hz, 2H), 3.91(t, J= 6.0Hz, 2H), 4.53(br s, 1H),5.35-5.42(m, 2H), 6.49(dd, J=8.4, 0.9Hz, 1H), 6.67-6.71(m, 2H),6.94-7.00(m, 2H), 7.29(dd, J=8.4, 2.4Hz, 1H), 7.93(dd, J=2.4, 0.9Hz,1H); IR (KBr): 3415, 3229, 1606, 1521, 1465, 1379, 1315, 1141, 985, 815cm⁻¹ Ib-315 mp 207-209° C.; ¹H NMR (CDCl₃) δ 1.76(s, 3H), 1.76(s, 3H),1.96(s, 6H), 1.98(s, 6H), 3.4(br s, 1H), 3.88(d, J=7.8Hz, 2H), 5.42(t,J=7.8Hz, 1H), 6.76-6.82(m, 2H), 6.92-6.98(m, 2H), 7.26(d, J=7.8Hz, 1H),7.34(dd, J= 7.8, 2.1Hz, 1H), 8.29(d, J=2.1Hz, 1H); IR (KBr): 3452, 3367,1619, 1517, 1457, 1353, 1280, 1176, 1107, 820, 540 cm⁻¹ Ib-316 mp156-158° C.; ¹H NMR (CDCl₃) δ 1.75(s, 3H), 1.76(s, 3H), 1.76(s, 3H),1.78(s, 3H), 1.97(s, 6H), 2.00(s, 6H), 3.75(d, J=6.6Hz, 2H), 3.88(d, J=7.7Hz, 2H), 5.40(t, J=6.6Hz, 2H), 5.42(t, J=7.7Hz, 1H), 6.68-6.73(m,2H), 6.93-7.00(m, 2H), 7.26(dd, J=8.1, 1.1Hz, 1H), 7.34(dd, J=8.1, 2.1Hz, 1H), 8.29(dd, J=2.1, 1.1Hz, 1H); IR (KBr): 3391, 1612, 1518, 1462,1180, 1108, 820, 807, 546 cm⁻¹. Ib-317 mp 161-164° C.; ¹H NMR (CDCl₃) δ1.77(s, 3H), 1.77(s, 3H), 1.99(s, 6H), 1.99(s, 6H), 2.11(s, 6H), 3.89(d,J=7.8Hz, 2H), 5.43(t, J=7.8Hz, 1H), 5.94(s, 2H), 7.21-7.39(m, 6H),8.31(dd, J=2.3, 0.8Hz, 1H); IR (KBr): 3439, 1586, 1520, 1449, 1406,1110, 999, 824, 750, 565 cm⁻¹ Ib-318 mp 137-138° C., ¹H NMR (CDCl₃) δ1.75(s, 3H), 1.78(s, 6H), 1.81(s, 3H), 1.82(s, 3H), 1.89(s, 6H), 1.98(s,6H), 2.15(s, 3H), 3.75(d, J=6.9Hz, 2H), 4.86(d, J=7.2Hz, 2H), 5.40(m,1H), 5.59(m, 1H), 6.64-6.71(m, 3H), 6.94-6.99(m, 2H), 7.26(d, J=8.4Hz,1H). IR (KBr): 3412, 2914, 1611, 1592, 1460, 1311, 1297, 1282, 1237 cm⁻¹Ib-319 mp 129-130° C., ¹H NMR (CDCl₃) δ 1.74(s, 3H), 1.79(s, 6H),1.82(s, 3H), 1.98(s, 6H), 1.99(s, 6H), 2.25(s, 3H), 3.75(d, J=6.9Hz,2H), 4.90(d, J= 6.6Hz, 2H), 5.40 (br t, J=6.9Hz, 1H), 5.59(br t,J=6.9Hz, 1H), 6.70(m, 2H), 6.97(m, 2H), 7.23 d,J=2.1Hz, 1H), 7.82d,J=2.1Hz, 1H) Ib-320 mp 153-154° C., ¹H NMR (CDCl₃) δ 1.75(s, 3H),1.79(s, 6H), 1.83(s, 3H), 1.89(s, 6H), 1.96(s, 3H), 1.99(s, 6H), 2.15(s,3H), 3.75(d, J=6.9Hz, 2H), 4.86(d, J=6.9Hz, 2H), 5.40(m, 1H), 5.58(m,1H), 6.69-6.73(m, 3H), 6.94-7.01(m, 2H), 7.84(s, 1H). IR (KBr): 3386,2928, 1608, 1518, 1464, 1377, 1315, 1180, 1122, 1028 cm⁻¹ Ib-321 mp115-117° C.; ¹H NMR (CDCl₃) δ 1.60(s, 3H), 1.73(s, 3H), 1.75(s, 3H),1.78(s, 3H), 1.95(s, 6H), 2.01(s, 6H), 3.60(d, J=7.7Hz, 2H), 3.91(t, J=6.0Hz, 2H), 4.52(m, 1H), 5.32-5.42(m, 2H), 6.49(d, J=8.4Hz, 1H), 7.05-7.11(m, 2H), 7.28(dd, J=8.4, 2.3Hz, 1H), 7.39-7.44(m, 2H), 7.91(d, J=2.3Hz, 1H): IR (KBr): 3425, 1609, 1541, 1391, 1378, 814, 550 cm⁻¹

 

TABLE 121 Ib-322 mp 119-122° C.; ¹H NMR (CDCl₃) δ 1.75(s, 3H), 1.77(s,3H), 1.78(s, 3H), 1.82(s, 3H), 2.01(s, 6H), 2.03(s, 3H), 3.34(s, 3H),3.91(dd, J=5.9, 5.9Hz, 2H), 4.51(t, J=5.2Hz, 1H), 4.64(d, J=6.7Hz, 2H),5.38(m, 1H), 5.57(m, 1H), 6.47(d, J=8.5Hz, 1H), 6.97-7.08(m, 3H),7.23-7.28(m, 1H), 7.72(d, J=1.8Hz, 1H); IR (nujor): 3325, 1926, 2853,1608, 1538, 1514, 1457, 1389, 1296, 1262, 1214, 1110, 1006 cm⁻¹ Ib-323¹H NMR (300 MHz, CDCl₃) δ 1.80(d, J=0.9Hz, 3H), 1.83(d, J=0.9Hz, 3H),1.98(s, 6H), 2.06(s, 3H), 3.32(s, 3H), 4.88(d, J=6.9Hz, 2H), 5.55-5.62(m, 1H), 6.80(d, J=7.8Hz, 2H), 6.85(dd, J=8.6, 0.8Hz, 1H), 7.11(d,J=7.8Hz, 2H), 7.40(dd, J=8.6, 2.6Hz, 1H), 7.98(dd, J=2.6, 0.8Hz, 1H)Ib-324 ¹H NMR (300 MHz, CDCl₃) δ 1.74(s, 3H), 1.78(s, 3H), 1.80(s, 3H),1.83(s, 3H), 1.98(s, 3H), 2.07(s, 3H), 3.33(s, 3H), 3.75(d, J=6.6Hz,2H), 4.88(d, J=6.9Hz, 2H), 5.36-5.43(m, 1H), 5.55-5.62(m, 1H), 6.71(d,J=8.0Hz, 2H), 6.84(dd, J=2.4, 0.8Hz, 1H), 7.30(d, J=8.0Hz, 2H), 7.40(dd,J=8.6, 2.4Hz, 1H), 7.98(dd, J=2.4, 0.8Hz, 1H) Ib-325 ¹H NMR (300 MHz,CDCl₃) δ 1.80(s, 3H), 1.83(s, 3H), 1.97(s, 6H), 2.06(s, 3H), 3.32(s,3H), 3.92(s, 3H), 4.46(s, 2H), 4.88(d, J=6.9Hz, 2H), 5.55- 5.62(m, 1H),6.71(d, J=8.0Hz, 2H), 6.84(d, J=8.4Hz, 1H), 7.12(d, J= 8.0Hz, 2H), 7.40H, dd, J=8.4, 2.2Hz, 1H), 7.50(d, J=8.1Hz, 2H), 7.98 (d, J=2.2Hz, 1H),8.04(d, J=8.1Hz, 2H) Ib-326 ¹H NMR (300 MHz, CDCl₃) δ 1.80(s, 3H),1.83(s 3H), 1.97(s, 6H), 2.06(s, 3H), 3.32(s, 3H), 4.48(s, 2H), 4.88(d,J=6.9Hz, 2H), 5.55-5.61(m, 1H), 6.70(d, J=7.8Hz, 2H), 6.85(d, J=8.4Hz,1H), 7.12(d, J=7.8Hz, 2H), 7.40(dd, J=8.4, 0.7Hz, 1H), 7.53(d, J=8.1Hz,2H), 7.99(d, J=0.7Hz, 1H), 8.11(d, J=8.1Hz, 2H) Ib-327 ¹H NMR (300 MHz,CDCl₃) δ 1.80(s, 3H), 1.83(s, 3H), 1.98(s, 3H), 2.07(s, 3H), 3.32(s,3H), 3.86(s, 3H), 3.87(s, 6H), 4.33(s, 2H), 4.88(s, J=6.6Hz, 2H),5.55-5.60(m, 1H), 6.67(s, 2H), 6.76(d, J=7.1Hz, 2H), 6.85(dd, J= 8.4,0.6Hz, 1H), 7.15(d, J=7.1Hz, 2H), 7.40(dd, J=8.4, 2.4Hz, 1H), 7.98 (dd,J=2.4, 0.6Hz, 1H) Ib-328 ¹H NMR (300 MHz, CDCl₃) δ 1.80(s, 3H), 1.83(s,3H), 1.97(s, 6H), 2.06(s, 3H), 3.31(s, 3H), 4.38(s, 2H), 4.88(d,J=7.2Hz, 2H), 5.55-5.62(m, 1H), 6.29(d, J=3.0Hz, 1H), 6.35(dd, J=3.0,1.8Hz, 1H), 6.77(d, J=8.1Hz, 2H), 6.84(dd, J=8.2, 0.6Hz, 1H), 7.14(d,J=8.1Hz, 2H), 7.399(dd, J= 1.8, 0.8Hz, 1H), 7.40(dd, J=8.2, 2.4Hz, 1H),7.98(dd, J=2.4, 0.6Hz, 1H) Ib-329 mp 110-111° C.; ¹H NMR (CDCl₃) δ1.80(s, 3H), 1.83(s, 3H), 1.98(s, 6H), 2.06(s, 3H), 3.33(s, 3H), 4.88(d,J=6.9Hz, 2H), 5.59(m, 1H), 6.79(d, J= 8.7Hz, 2H), 6.84(dd, J=8.4 andJ=0.9Hz, 1H), 6.95(d, J=7.2Hz, 2H), 7.56(dd, J=8.4 and 2.7Hz, 1H),8.11(dd, J=2.4 and 0.6Hz, 1H); IR (CHCl₃): 3462, 3016, 2934, 1620, 1604,1279, 1241, 1087, 982, cm⁻¹. Ib-330 mp 115-116° C.; ¹H NMR (CDCl₃) δ1.74(s, 3H), 1.78(s, 3H), 1.80(s, 3H), 1.83(s, 3H), 2.00(s,6H), 2.06(s,3H) 3.33(s, 3H), 3.75(d, J=6.6Hz, 2H), 4.88(d, J=6.9Hz, 2H), 5.39(m,1H), 5.59(m, 1H), 6.71(d, J=7.8Hz, 2H), 6.84(dd, J=8.4 and 0.6Hz, 1H),6.97(d, J=7.5Hz, 2H), 7.56(dd, J=8.4 and 2.4Hz, 1H), 8.11(dd, J=2.4 and0.9Hz, 1H); IR (CHCl₃): 3424, 3004, 2975, 2934, 2860, 1612, 1491, 1402,1377, 1280, 1241, cm⁻¹.

 

TABLE 122 Ib-331 mp 111-112° C.; ¹H NMR (CDCl₃) δ 1.26(s, 3H), 1.28(s,3H), 1.79(s, 3H), 1.83(s, 3H), 2.00(s,6H), 2.06(s, 3H), 3.33(s, 3H),3.68(m, 1H), 4.88(d, J= 6.9Hz, 2H), 5.59(m, 1H), 6.67(d, J=8.4Hz, 2H),6.84(dd, J=8.4 and 6.0 Hz, 1H), 6.95(d, J=7.2Hz, 2H), 7.56(dd, J=8.4 and2.4Hz, 1H), 8.12(dd, J=2.4 and 0.6Hz, 1H); IR (CHCl₃): 3423, 3018, 2975,2934, 2872, 1612, 1354, 1317, 1377, 1280, 1242, cm⁻¹. Ib-332 mp 139-140°C.; ¹H NMR (CDCl₃) δ 1.14-1.46(m 5H), 1.65-1.80(m 3H), 1.82 (s, 3H),1.83(s, 3H), 2.00(s, 6H), 2.06(s, 3H), 3.33(s, 3H), 2.10-2.15(m, 2H),3.30(m, 1H), 4.88(d, J=7.2Hz, 2H), 5.59(m, 1H), 6.87(d, J=8.7Hz, 2H),6.84(dd, J=8.7 and 0.9Hz, 1H), 6.94(d, J=7.2Hz, 2H), 7.56(dd, J= 8.7 and2.7Hz, 1H), 8.11(dd, J=2.7 and 0.9Hz, 1H); IR (CHCl₃): 3422, 3002, 2933,2856, 1612, 1354, 1318, 1280, 1242, 1130, 1087, cm⁻¹. Ib-333 mp 155-156°C.; ¹H NMR (CDCl₃) δ 1.80(s, 3H), 1.83(s, 3H), 1.99(s, 6H), 2.06(s, 3H),3.33(s, 3H), 4.38(s, 2H), 4.89(d, J=6.9Hz, 2H), 5.59(m, 1H), 6.30(m,1H), 6.35-6.37(m, 1H), 6.77(d, J =8.4Hz, 2H), 6.83(dd, J=8.4 and 0.9Hz,1H), 6.98(d, J=7.5Hz, 2H), 7.40(dd, J=2.1 and 0.9Hz, 1H) 7.57(dd, J=8.7and 2.7Hz, 1H) 8.12(dd, J =2.4 and 0.6Hz, 1H); IR (CHCl₃): 3424, 2934,2861, 1613, 1280, 1241, 1217, cm⁻¹. Ib-334 mp 142-145° C.; ¹H NMR(CDCl₃) δ 1.99(s, 3H), 2.06(s, 3H), 3.33(s, 3H), 3.79 (brs, 2H), 5.40(s,2H), 6.40(dd, J=2.0, 3.2Hz, 1H), 6.49(d, J=3.3Hz, 1H), 6.78(d, J=8.4Hz,2H), 6.87(dd, J=0.8, 8.3Hz, 1H), 6.95(brd, J=7.2Hz, 2H), 7.47(dd, J=0.9,1.5Hz, 1H), 7.58(dd, J=2.6, 8.6Hz, 1H), 8.13(dd, J=0.8, 2.6Hz, 1H); IR(nujor): 3342, 2924, 2854, 1611, 1523, 1493, 1458, 1283, 1011, 824 cm⁻¹Ib-335 mp 158-159° C.; ¹H NMR (CDCl₃) δ 1.80(s, 3H), 1.83(s, 3H),2.00(s, 6H), 2.06(s, 3H), 3.33(s, 3H), 4.38(s, 2H), 4.89(d, J=7.0Hz,2H), 5.59(m, 1H), 6.74(d, J=8.6Hz, 2H), 6.84(dd, J=0.7, 8.4Hz, 1H),6.98(brd, J=6.9Hz, 2H), 7.28-7.46(m, 5H), 7.56(dd, J=2.5, 8.5Hz, 1H),8.12(dd, J=0.7, 2.3Hz, 1H), IR (nujor): 3357, 2926, 2854, 1613, 1526,1491, 1452, 1279, 1090, 997, 823, 732 cm⁻¹ Ib-336 mp 116-117° C.; ¹H NMR(CDCl₃) δ 1.80(s, 3H), 1.83(s, 3H), 2.00(s, 6H), 2.06(s, 3H), 2.30(s,3H), 3.33(s, 3H), 4.31(s, 2H), 4.88(d, J=6.9Hz, 2H), 5.59(m, 1H),5.93(m, 1H), 6.17(d, J=3.1Hz, 1H), 6.76(d, J=8.6Hz, 2H), 6.84(d,J=8.5Hz, 1H), 6.98(brd, J=6.7Hz, 2H), 7.56(dd, J=2.3, 8.5Hz, 1H),8.12(d, J=2.3Hz, 1H), IR (nujor): 3349, 2925, 2854, 1611, 1525, 1490,1455, 1280, 1240, 979, 822, 782 cm⁻¹ Ib-337 mp 94-97° C.; ¹H NMR (CDCl₃)δ 1.66(brd, J=6.7Hz; 3H), 1.73(s, 3H), 1.80 (s, 3H), 1.83(s, 3H),1.99(s, 6H), 2.06(s, 3H), 3.33(s, 3H), 3.69(brs, 2H), 4.88(d, J=6.9Hz,2H), 5.52-5.62(m, 2H), 6.70(d, J=8.6Hz, 2H), 6.83(dd, J=0.7, 8.4Hz, 1H),6.95(brd, J=7.4Hz, 2H), 7.56(dd, J=2.5, 8.5Hz, 1H), 8.11(dd, J=0.7,2.3Hz, 1H), IR (KBr): 3409, 3325, 2927, 2857, 1612, 1523, 1457, 1279,1085, 1002, 986, 820 cm⁻¹ Ib-338 mp 161-163° C.; ¹H NMR (CDCl₃) δ1.80(s, 3H), 1.83(s, 3H), 2.00(s, 6H), 2.06(s, 3H), 3.33(s, 3H), 3.86(s,3H), 3.87(s, 6H), 4.42(s, 2H), 4.88(d, J=7.0Hz, 2H), 5.59(m, 1H),6.66(s, 2H), 6.75(d, J=8.6Hz, 2H), 6.84(dd, J=0.6, 8.5Hz, 1H), 6.99(brd,J=6.7Hz, 2H), 7.56(dd, J=2.4, 8.4Hz, 1H), 8.12(dd, J=0.6, 2.3Hz, 1H), IR(KBr): 3373, 2934, 2831, 1604, 1592, 1522, 1457, 1280, 1240, 1124, 981,822 cm⁻¹

 

TABLE 123 Ib-339 mp 113-115° C.; ¹H NMR (CDCl₃) δ 1.74(s, 3H), 1.78(s,3H), 1.80(d, J=0.9Hz, 3H), 2.00(s, 6H), 2.06(s, 3H), 3.33(s, 3H),3.75(d, J=6.7Hz, 2H), 4.83(dd, J=5.3Hz, 2H), 5.39(m, 1H), 5.78-5.96(m,2H), 6.70(d, J=8.6Hz, 2H), 6.84(dd, J=0.7, 8.5Hz, 1H), 6.97(brd,J=7.3Hz, 2H), 7.57(dd, J=2.4, 8.4Hz, 1H), 8.11(dd, J=0.7, 2.4Hz, 1H); IR(njor): 3367, 2924, 2853, 1611, 1520, 1457, 1278, 1241, 992, 820 cm⁻¹Ib-340 mp 90-92° C.; ¹NMR (CDCl₃) δ 1.75(s, 3H), 1.78(s, 3H), 2.00(s,6H), 2.06 (s, 3H), 2.59(dt, J=6.7, 6.7Hz), 3.33(s, 3H), 3.75(d, J=6.9Hz,2H), 4.42(t, J=6.8Hz, 2H), 5.12(brd, J=10.2Hz, 1H), 5,20(ddt, J=1.6,1.6, 17.2Hz, 1H), 5.39(m, 1H), 5.96(ddt, J=6.7, 10.3, 17.1Hz, 1H),6.70(d, J=8.6Hz, 2H), 6.83(dd, J=0.7, 8.4Hz, 1H), 6.96(brd, J=6.9Hz,2H), 7.57(dd, J=2.3, 8.5Hz, 1H), 8.11(dd, J=07, 2.4Hz, 1H); IR (nujor):3362, 2952, 2925, 2854, 1611, 1604, 1519, 1466, 1280, 819 cm⁻¹ Ib-341 mp97-98° C.; ¹H NMR (CDCl₃) δ 1.04(t, J=7.5Hz, 3H), 1.75(s, 3H), 1.78(s,3H), 2.00(s, 6H), 2.06(s, 3H), 2.22(dq, J=7.0, 7.1Hz, 2H), 3.33(s, 3H),3.75 (d, J=6.9Hz, 2H), 4.95(d, J=5.3Hz, 2H), 5.39(m, 1H), 5.71(dt,J=6.1, 11.0Hz, 1H), 5.75(dt, J=6.1, 10.8Hz, 1H), 6.70(d, J=8.8Hz, 2H),6.84(dd, J=0.7, 8.5Hz, 1H), 6.97(brd, J=6.9Hz, 2H), 7.57(dd, J=2.4,8.4Hz, 1H), 8.12(dd, J=0.7, 2.5Hz, 1H), IR (KBr): 3341, 2965, 2930,1612, 1523, 1491, 1456, 1281.1243, 1089, 991, 822 cm⁻¹ Ib-342 mp129-130° C.; ¹H NMR (CDCl₃) δ 1.74(s, 3H), 1.78(s, 3H), 1.92(t, J=2.1 Hz3H), 2.00(s, 6H), 2.05(s, 3H), 3.32(s, 3H), 3.75(d, J=6.6Hz, 2H),5.02(m, 2H), 5.40(m, 1H), 6.72(d, J=8.4Hz, 2H), 6.89(dd, J=8.4 and 0.6Hz, 1H), 6.97(d, J=7.2Hz, 2H), 7.59(dd, J=8.4 and 2.4Hz, 1H), 8.12(dd,J=2.4 and 0.6Hz, 1H); IR (CHCl3): 3424, 3004, 2933, 2858, 1612, 1346,1279, 1241, cm⁻¹. Ib-343 mp 137-138° C.; ¹H NMR (CDCl₃) δ 1.75(s, 3H),1.78(s, 3H), 2.00(s, 6H), 2.06(s, 3H), 3.33(s, 3H), 3.75(d, J=6.9Hz,2H), 5.40(m, 3H), 6.40(dd, J= 3.3 and 1.8Hz, 1H), 6.49(d, J=3.3Hz, 1H),6.70(d, J=8.7Hz, 2H), 6.87 (dd, J=9.0 and 0.6Hz, 1H), 6.97(d, J=7.5Hz,2H), 7.47(dd, J=1.8 and 0.9Hz, 1H), 7.59(dd, J=8.4 and 2.4Hz, 1H),8.13(dd, J=2.4 and 0.6Hz, 1H); IR (CHCl₃): 3424, 3004, 2933, 2860, 1612,1402, 1453, 1346, 1280, cm⁻¹. Ib-344 mp 144-146° C.; ¹H NMR (CDCl₃) δ1.80(s, 3H), 1.84(s, 3H), 1.85(t, J=2.4Hz, 3H), 2.00(s, 6H), 2.07(s,3H), 3.34(s, 3H), 3.94(q, J=2.4Hz, 2H), 4.89(d, J=6.9Hz, 2H), 5.60(m,1H), 6.76(d, J=8.4Hz, 2H), 6.85(d, J=8.4Hz, 1H), 7.00(brd, J=7.5Hz, 2H),7.57(dd, J=2.4, 8.4Hz, 1H), 8.13(d, J=2.4Hz, 1H); IR (CHCl₃): 3451,3395, 3024, 3015, 2934, 1621, 1604, 1518, 1491, 1280, 993, 825 cm⁻¹Ib-345 mp 113-115° C.; ¹H NMR (CDCl₃) δ 1.75(s, 3H), 1.77(s, 3H),2.00(s, 6H), 2.05(s, 3H), 3.32(s, 3H), 3.75(d, J=6.7Hz, 2H), 4.64(dd,J=3.9, 29.2Hz, 1H), 4.66(dd, J=2.9, 29.2Hz 1H), 4.81(dd, J=3.0, 47.5Hz,1H), 4.82(dd, J=3.9, 47.4Hz, 1H), 5.40(m 1H), 6.70(d, J=8.6Hz, 2H),6.90(dd.J=0.7, 8.4Hz.1H), 6.96(brd, J=7.5Hz, 2H), 7.59(dd, J=2.4, 8.4Hz,1H), 8.09(dd, J=0.7, 2.5Hz, 1H); IR (nujor): 3399, 2925, 2854, 1612,1519, 1491, 1450, 1283, 1087, 929 cm⁻¹

 

TABLE 124 Ib-346 mp 111-112° C.; ¹H NMR (CDCl₃) δ 1.75(s, 3H), 1.78(s,3H), 2.00(s, 6H), 2.05(s, 3H), 3.32(s, 3H), 3.75(d, J=6.9Hz, 2H),4.82(dq, J=1.4, 8.6Hz, 2H), 5.39(m, 1H), 6.70(d, J=8.7Hz, 2H),6.93-6.97(m, 3H), 7.64(dd, J=2.4, 8.4Hz, 1H), 8.10(dd, J=0.3, 2.1Hz,1H), IR (KBr): 3407, 2931, 2860, 1613, 1521, 1292, 1274, 1259, 1240,1164, 1070, 823 cm⁻¹ Ib-347 mp 154-156° C.; ¹H NMR (CDCl₃) δ 1.85(t,J=2.6Hz, 3H), 1.99(s, 6H), 2.06 (s, 3H), 3.33(s, 3H), 3.93(q, J=2.4Hz,2H), 5.40(s, 2H), 6.40(dd, J=1.7, 3.2Hz, 1H), 6.49(dd, J=0.9, 3.0Hz,1H), 6.76(d, J=8.7Hz, 2H), 6.87(dd, J=0.9, 8.7Hz, 1H), 6.99(brd,J=7.5Hz, 2H), 7.48(dd, J=0.9, 1.8Hz, 1H), 7.58(dd, J=2.6, 8.6Hz, 1H),8.14(dd, J=0.6, 2.4Hz, 1H), IR (KBr): 3410, 2989, 2934, 2860, 1610,1520, 1278, 1242, 992, 822, 742 cm⁻¹ Ib-348 mp 165-168° C.; ¹H NMR(CDCl₃) δ 1.85(t, J=2.4Hz, 3H), 1.91(t, J=2.4Hz, 3H), 1.99(s, 6H),2.05(s, 3H), 3.32(s, 3H), 3.93(q, J=2.4Hz, 2H), 5.01(q, J=2.4Hz, 2H),6.76(d, J=8.7Hz, 2H), 6.89(dd, J=0.8, 8.6Hz, 1H), 6.99(brd, J=7.2Hz,2H), 7.58(dd, J=2.4, 8.4Hz, 1H), 8.12(dd, J=0.6, 2.4Hz, 1H), IR (KBr):3393, 3338, 2923, 2862, 2237, 1612, 1604, 1521, 1279, 1243, 996, 824cm⁻¹ Ib-349 mp 172-173° C.; ¹H NMR (CDCl₃) δ 1.74(s, 3H),, 1.78(s, 3H),2.05(s, 3H), 2.30(s, 6H), 2.63(s, 3H), 3.32(s, 3H), 2.30(s, 6H), 3.74(d,J=6.6Hz, 2H), 5.39(m, 1H), 6.70(d, J=8.7Hz, 2H), 6.96(d, J=6.6Hz, 2H),7.27(dd, J= 8.4 and 0.6Hz, 1H), 7.51(dd, J=8.1 and 2.1Hz, 1H), 7.42(dd,J=2.1 and 0.9Hz, 1H), IR (CHCl₃): 3423, 3003, 2931, 28598, 1613, 1589,1315, 14021, 1289, cm⁻¹. Ib-350 mp 183-184° C.; ¹H NMR (CDCl₃) δ 1.75(s,3H), 1.79(s, 3H), 2.01(s, 6H), 2.03(s, 3H), 3.32(s, 3H), 3.33(s, 3H),3.75(d, J=6.9Hz, 2H), 5.40(m, 1H), 6.72(d, J=8.7Hz, 2H), 6.75(d,J=8.1Hz, 2H), 7.98(dd, J=8.1 and 2.1Hz, 1H), 8.17(dd, J=8.1 and 0.9Hz,1H), 8.70(dd, J=2.7 and 0.6Hz, 1H),; IR (CHCl₃): 3424, 3016, 2934, 2860,1613, 1315, 1292, 1231, cm⁻¹. Ib-351 mp 148-149° C.; ¹H NMR (CDCl₃) δ1.79(s, 3H), 1.83(s, 3H), 2.05(s, 3H), 2.06(s, 3H), 3.33(s, 3H), 3.34(s,3H), 4.88(d, J=6.9Hz, 2H), 5.58(m, 1H), 6.78(d, J=8.7Hz, 2H), 6.84(d,J=8.4Hz, 1H), 7.1 1(d, J=8.7Hz, 2H), 7.56 (dd, J=8.4, 2.4Hz, 1H),8.12(d, J=2.4Hz, 1H) IR (KBr): 3393, 1603, 1520, 1492, 1459, 1399, 1373,1357, 1282, 1247, 1128, 1038, 1020, 982, 824 cm⁻¹ Ib-352 mp 106-107° C.;¹H NMR (CDCl₃) δ 1.75(s, 3H), 1.78(s, 3H), 1.80(s, 3H), 1.83(s, 3H),2.07(s, 3H), 2.08(s, 3H), 3.33(s, 3H), 3.34(s, 3H), 3.75(d, J= 6.6Hz,2H), 4.88(d, J=7.2Hz, 2H), 5.38(m, 1H), 5.58(m, 1H), 6.70(d, J= 8.4Hz,2H), 6.84(d, J=8.4Hz, 1H), 7.12(d, J=8.4Hz, 2H), 7.56(dd, J= 8.4, 2.4Hz,1H), 8.12(d, J=2.4Hz, 1H) IR (KBr): 3401, 1614, 1603, 1561, 1522, 1491,1463, 1281, 1242, 1182, 1128, 1037, 985, 821 cm⁻¹ Ib-353 mp 126-127° C.;¹H NMR (CDCl₃) δ 1.49(s, 3H), 1.67(s, 3H), 1.80(s, 3H), 1.83(s, 3H),2.02(s, 3H), 2.07(s, 3H), 2.81(d, J=5.4Hz, 3H), 3.30(s, 3H), 3.34(s,3H), 4.17(q, J=5.4Hz, 2H), 4.27(d, J=7.2Hz, 2H), 4.89(d, J= 7.2Hz, 2H),5.29(m, 1H), 5.58(m, 1H), 6.85(d, J=8.4Hz, 1H), 7.32(d, J= 4.2Hz, 2H),7.44(d, J=4.2Hz, 2H), 7.59(dd, J=8.4, 2.4Hz, 1H), 8.11(d, J= 2.4Hz, 1H)IR (KBr): 3304, 1603, 1564, 1512, 1491, 1455, 1355, 1329, 1279, 1149,1131, 1043, 1019, 986, 879, 823, 583 cm⁻¹

 

TABLE 125 Ib-354 mp 117-118° C.; ¹H NMR (300 MHz, CDCl₃) δ 1.12-1.30(m,2H), 1.30-1.48 (m, 2H), 1.62-1.75(m, 2H), 1.80(s, 3H), 1.83(s, 3H),1.75-1.84(m, 2H), 2.06 (s, 3H), 2.07(s, 3H), 2.06-2.18(m, 2H), 3.33(s,3H), 3.34(s, 3H), 3.30-3.37 (m, 1H), 4.88(d, J=6.9Hz, 2H), 5.56-5.61(m,1H), 6.65-6.72(m, 2H), 6.84 (dd, J=8.7, 0.9Hz, 1H), 706-7.13(m, 2H),7.56(dd, J=8.7, 2.4Hz, 1H), 8.11(dd, J=2.4, 0.9Hz, 1H). Ib-355 mp108-110° C., ¹H NMR (CDCl₃) δ 1.74(s, 3H), 1.78(s, 3H), 1.81(s, 3H),1.82(s, 3H), 1.94(s, 3H), 2.06(s, 3H), 2.26(s, 3H), 3.32(s, 3H), 3.33(s,3H), 3.75(d, J=6.9Hz, 2H), 4.87(d, J=7.2Hz, 2H), 5.40(m, 1H), 5.57(m,1H), 6.65(d, J=8.4Hz, 2H), 6.72(d, J=8.4Hz, 2H), 7.14(d, J=8.4Hz, 2H),7.37(d, J=8.4Hz, 1H). IR (KBr): 3417, 2930, 1613, 1595, 1520, 1449,1391, 1297, 1281, 1246, 1133, 1101, 1038 cm⁻¹ Ib-356 mp 119-121° C., ¹HNMR (CDCl₃) δ 1.74(s, 3H), 1.78(s, 3H), 1.79(s, 3H), 1.82(s, 3H),2.06(s, 3H), 2.07(s, 3H), 2.25(s, 3H), 3.33(s, 3H), 3.35(s, 3H), 3.75(d,J=6.6Hz, 2H), 4.91(d, J=6.6Hz, 2H), 5.39(br t, J=6.6Hz, 1H), 5.59(br t,J=6.6Hz, 1H), 6.71(d, J=8.4Hz, 2H), 7.13(d, J=8.4Hz, 2H), 7.37(d,J=2.1Hz, 1H), 7.94(d, J=2.1Hz, 1H) Ib-357 mp 130-132° C., ¹H NMR (CDCl₃)δ 1.74(s, 3H), 1.79(s, 6H), 1.82(s, 3H), 1.94(s, 3H), 2.06(s, 6H),3.33(s, 3H), 3.37(s, 3H), 3.76(d, J=6.9Hz, 2H), 4.86(d, J=6.9Hz, 2H),5.40(m, 1H), 5.57(m, 1H), 6.71-6.74(m, 3H), 7.14 (d, J=8.7Hz, 2H),7.94(s, 1H). IR (KBr): 3392, 2927, 1611, 1521, 1448, 1390, 1349, 1322,1286, 1270, 1236, 1179, 1115, 1026 cm⁻¹ Ib-358 mp 120-121° C.; ¹H NMR(CDCl₃) δ 1.74(s, 3H), 1.78(s, 3H), 2.06(s, 3H), 2.07(s, 3H), 2.63(s,3H), 3.33(s, 6H), 3.75(d, J=9.6Hz, 2H), 5.39(m, 1H), 6.70(d, J=8.4Hz,2H), 7.12(d, J=8.4Hz, 2H), 7.27(d, J=8.1Hz, 1H), 7.51 (dd, J=8.1, 2.4Hz,1H), 8.42(d, J=2.4Hz, 1H) IR (KBr): 3379, 1614, 1587, 1523, 1459, 1395,1351, 1319, 1286, 1136, 1109, 1038, 1016, 985, 818 cm⁻¹ Ib-359 mp163-164° C.; ¹H NMR (300 MHz, CDCl₃) δ 1.75(s, 3H), 1.78(s, 3H), 2.07(s, 3H), 2.09(s, 3H), 3.33(s, 3H), 3.36(s, 3H), 3.75(d, J=6.6Hz, 2H),3.91 (t, J=5.9Hz, 2H), 4.58(br s, 1H), 5.35-5.42(m, 2H), 6.49(d,J=8.3Hz, 1H), 6.65-6.72(m, 2H), 7.08-7.15(m, 2H), 7.44(dd, J=8.3, 2.0Hz,1H), 8.06(d, J=2.0Hz, 1H). Ib-360 mp 145-146° C.; ¹H NMR (300 MHz,CDCl₃) δ 1.79(s, 3H), 2.06(s, 3H), 2.08 (s, 3H), 3.35(s, 3H), 3.78(t,J=5.6Hz, 2H), 3.88(br s, 1H), 4.53(br s), 5.36-5.44(m, 1H), 6.61(dd,J=8.4, 0.75Hz, 1H), 6.73-6.79(m, 1H), 6.92- 6.98(m, 2H), 7.45(dd, J=8.4,2.1Hz, 1H), 8.04(d, J=2.1Hz, 1H). Ib-361 mp 143-144° C.; ¹H NMR (300MHz, CDCl₃) δ 1.75(s, 3H), 1.79(s, 3H), 2.06 (s, 3H), 2.09(s, 3H),3.35(s, 3H), 3.36(s, 3H), 3.78(t, J=6.0Hz, 2H), 3.83-3.94(m, 3H),4.53(br s, 1H), 5.34-5.44(m, 2H), 6.48(dd, J=8.4, 0.9 Hz, 1H),6.73-6.79(m, 1H), 6.92-6.98(m, 2H), 7.43(dd, J=8.4, 2.4Hz, 1H), 8.05(dd,J=2.4, 0.6Hz, 1H). Ib-362 ¹H NMR (300 MHz, CDCl₃) δ 1.20-1.35(m, 3H),1.35-1.48(m, 2H), 1.77(s, 3H), 1.82(s, 3H), 1.60-1.96(m, 3H), 2.04(s,3H), 2.09(s, 3H), 2.04-2.15(m, 2H), 3.34(s, 3H), 3.36(s, 3H),3.53-3.64(m, 1H), 4.64(d, J=6.9Hz, 2H), 4.60-4.65(m, 1H), 5.54-560(m,1H), 6.47(d, J=8.4Hz, 1H), 6.96-7.09(m, 3H), 7.41(dd, J=8.4.2.2Hz, 1H),8.02(d, J=2.2Hz, 1H).

 

TABLE 126 Ib-363 mp 96-97° C.; ¹H NMR (CDCl₃) δ 1.74(s, 3H), 1.79(s,6H), 1.82(s, 3H), 2.05 (s, 6H), 2.18(s, 3H), 3.74(d, J=6.6Hz, 2H),4.87(d, J=7.2Hz, 2H), 5.39(t, J=6.9Hz, 1H), 5.58(t, J=7.2Hz, 1H),6.70(d, J=8.4Hz, 2H), 6.81(d, J= 8.4Hz, 1H), 6.96-6.99(m, 3H), 7.57(dd,J=0.9, 8.7Hz, 1H), 8.16(d, J= 2.1Hz, 1H); IR (KBr): 3345, 2972, 2913,1613, 1560, 1522, 1490, 1466, 1281, 1240, 982, 827 cm⁻¹ Ib-364 mp133-134° C.: ¹H NMR (CDCl₃) δ 1.79(s, 3H), 1.82(s, 3H), 2.05(s, 6H),2.18(s, 3H), 4.17(br s, 1H), 4.38(s, 2H), 4.87(d, J=7.2Hz, 2H), 5.58(t,J= 7.2Hz, 1H), 6.74(d, J=8.4Hz, 2H), 6.81(dd, J=0.6, 8.4Hz, 1H),6.97-6.99 (m, 3H), 7.31-7.46(m, 5H), 7.57(dd, J=2.7, 8.7Hz, 1H),8.15(dd, J=0.6, 2.4Hz, 1H); IR (KBr): 3357, 2962, 2922, 1614, 1526,1491, 1465, 1359, 1280, 1241, 999, 828 cm⁻¹ Ib-365 mp 89-91° C.; ¹H NMR(CDCl₃) δ 1.71(s, 3H), 1.75(s, 3H), 1.79(s, 3H), 1.82 (s, 3H), 2.25(s,3H), 3.75(d, J=6.9Hz, 2H), 3.88(s, 3H), 4.87(d, J=6.9Hz, 2H), 5.37(m,1H), 5.58(m, 1H), 6.74-6.84(m, 4H), 7.21(s, 1H), 7.41- 7.45(m, 2H),7.76(dd, J=2.4, 8.4Hz, 1H), 8.19(d, J=2.4Hz, 1H); IR (CHCl₃): 3426,2935, 2859, 1611, 1524, 1504, 1482, 1379, 1357, 1316, 1281, 1241, 1187,1165, 1128, 1039, 979, 895 cm⁻¹ Ib-366 mp 93-94° C.; ¹H NMR (CDCl₃) δ1.25(d, J=6.3Hz, 6H), 1.79(s, 3H), 1.82(s, 3H), 2.24(s, 3H), 3.67(m,1H), 3.79(s, 3H), 4.87(d, J=7.2Hz, 2H), 5.57(m, 1H), 6.69(d, J=7.5Hz,2H), 6.79(s, 1H), 6.82(d, J=8.4Hz, 1H), 7.21(s, 1H), 7.42(d, J=8.4Hz,2H), 7.60(dd, J=2.4, 8.7Hz, 1H), 8.19(d, J=2.4Hz, 1H); IR (CHCl₃): 3424,2974, 2934, 2871, 1673, 1611, 1566, 1524, 1504, 1482, 1385, 1357, 1318,1281, 1242, 1129, 1039, 979 cm⁻¹ Ib-367 mp 105-108° C.; ¹H NMR (CDCl₃) δ1.79(s, 3H), 1.82(s, 3H), 2.24(s, 3H), 3.78(s, 3H), 4.38(s, 2H), 4.87(d,J=7.2Hz, 2H), 5.57(m, 1H), 6.73(d, J=8.4Hz, 2H), 6.79(s, 1H), 6.82(d,J=8.4Hz, 1H), 7.20(s, 1H), 7.28-7.43(m, 7H), 7.60(dd, J=2.4, 8.4Hz, 1H),8.18(d, J=2.4Hz, 1H); IR (CHCl₃): 3448, 3421, 2936, 2859, 1612, 1566,1524, 1482, 1391, 1358, 1316, 1281, 1242, 1187, 1165, 1128, 1039, 979cm⁻¹ Ib-368 mp 112-113° C.; ¹H NMR (CDCl₃) δ 1.55-1.72(m, 6H), 1.79(s,3H), 1.82(s, 3H), 2.07-2.12(m, 2H), 2.24(s, 3H), 3.41(m, 1H), 3.79(s,3H), 3.96(s, 4H), 4.87(d, J=6.6Hz, 2H), 5.57(m, 1H), 6.70-6.83(m, 4H),7.20(s, 1H), 7.42(d, J=8.4Hz, 2H), 7.42(d, J=8.4Hz, 2H), 7.60(dd, J=1.8,8.4Hz, 1H), 8.18(d, J=1.8Hz, 1H); IR (CHCl₃): 3425, 2952, 2887, 1611,1524, 1504, 1482, 1445, 1376, 1357, 1310, 1281, 1188, 1152, 1105, 1036,977, 925 cm⁻¹ Ib-369 mp 141-142° C.; ¹H NMR (CDCl₃) δ 1.56(m, 2H),1.79(s, 3H), 1.82(s, 3H), 2.05-2.10(m, 2H), 225(s, 3H), 3.48-3.59(m,3H), 3.79(s, 3H), 4.00-4.05(m, 2H), 4.87(d, J=6.9Hz, 2H), 5.57(m, 1H),6.73-6.84(m, 4H), 7.20(s, 1H), 7.42(d, J=8.4Hz, 2H), 7.60(dd, J=2.4,8.4Hz, 1H), 8.18(d, J=2.4Hz, 1H); IR (CHCl₃): 3424, 2966, 2939, 2850,1611, 1566, 1523, 1482, 1386, 1357, 1316, 1188, 1136, 1087, 1039, 982,870 cm⁻¹ Ib-370 mp 83-86° C.; ¹H NMR (CDCl₃) δ 1.71(s, 3H), 1.75(s, 3H),2.24(s, 3H), 3.74-3.81(m, 5H), 5.35-5.40(m, 3H), 6.40(m, 1H), 6.48(m,1H), 6.74(d, J=8.7Hz, 2H), 6.80(s, 1H), 6.85(d, J=8.7Hz, 1H), 7.21(s,1H), 7.42-7.48(m, 3H), 7.62(dd, J=2.4, 8.4Hz, 1H), 8.20(d, J=2.4Hz, 1H);IR (CHCl₃): 3427, 2935, 2858, 1611, 1567, 1524, 1503, 1480, 1390, 1346,1316, 1282, 1187, 1165, 1150, 1127, 1039, 1015, 992, 920 cm⁻¹

 

TABLE 127 Ib-371 mp 100-101° C.; ¹H NMR (CDCl₃) δ 1.26(d, J=6.3Hz, 6H),2.24(s, 3H), 3.67(m, 1H), 3.79(s, 3H), 5.39(s, 2H), 6.40(m, 1H), 6.49(m,1H), 6.70-6.73 (m, 2H), 6.79(s, 1H), 6.84(d, J=8.4Hz, 1H), 7.21(s, 1H),7.43(d, J=8.4Hz, 2H), 7.48(m, 1H), 7.62(dd, J=2.4, 8.4Hz, 1H), 8.20(d,J=2.4Hz, 1H); IR (CHCl₃): 3424, 2967, 2934, 1611, 1567, 1524, 1479,1384, 1346, 1318, 1282, 1243, 1187, 1151, 1127, 1039, 1015, 992, 920cm⁻¹ Ib-372 mp 138-139° C.; ¹H NMR (CDCl₃) δ 1.56-1.84(m, 6H),2.09-2.12(m, 2H), 2.24(s, 3H), 3.42(m, 1H), 3.79(s, 3H), 3.97(s, 4H),5.39(s, 2H), 6.40(m, 1H), 6.49(d, J=3.3Hz, 1H), 6.72(m, 2H), 6.79(s,1H), 6.85(d, J=8.7Hz, 1H), 7.20(s, 1H), 7.42(d, J=8.7Hz, 2H), 7.47(d,J=1.8Hz, 1H), 7.62(dd, J=2.7, 8.7Hz, 1H), 8.20(d, J=2.7Hz, 1H); IR(CHCl₃): 3425, 2952, 2886, 1611, 1568, 1524, 1504, 1480, 1446, 1375,1346, 1311, 1282, 1188, 1151, 1105, 1037, 993, 924 cm⁻¹ Ib-373 mp128-130° C.; ¹H NMR (CDCl₃) δ 1.73(s, 3H), 1.78(s, 3H), 1.79(s, 3H),1.82(s, 3H), 2.04(s, 3H), 2.08(s, 3H), 3.34(s, 3H), 3.54(s, 3H), 3.75(d,J= 6.3Hz, 2H), 4.86(d, J=6.9Hz, 2H), 5.39(m, 1H), 5.56(m, 1H), 6.72(d,J= 8.4Hz, 2H), 6.79(dd, J=8.7, 0.6Hz, 1H), 7.11(d, J=8.4Hz, 2H),7.48(dd, J= 8.7, 2.4Hz, 1H), 8.04(dd, J=2.4, 0.6Hz, 1H); IR (KBr) 3420,1730, 1612, 1603, 1561, 1521, 1490, 1461, 1277, 1223, 1120, 1002, 983,823 cm⁻¹ Ib-374 mp 172-173° C.; ¹H NMR (CDCl₃) δ 1.73(s, 3H), 1.77(s,3H), 2.04(s, 3H), 2.08(s, 3H), 3.35(s, 3H), 3.53(s, 3H), 3.75(d,J=6.9Hz, 2H), 5.38(s, 2H), 5.39(m, 1H), 6.39(dd, J=3.3, 1.8Hz, 1H),6.48(d, J=3.3Hz, 1H), 6.73(d, J= 8.4Hz, 2H), 6.82(dd, J=8.4, 0.9Hz, 1H),7.11(d, J=8.4Hz, 2H), 7.47(dd, J=1.8, 0.9Hz, 1H) 7.50(dd, J=8.4, 2.4Hz,1H), 8.06(dd, J=2.4, 0.9Hz, 1H); IR (KBr) 3415, 1730, 1610, 1562, 1520,1490, 1452, 1346, 1278, 1224, 1121, 989, 825, 736 cm⁻¹ Ib-375 mp146-147° C.; ¹H NMR (CDCl₃) δ 1.75(s, 3H), 1.78(s, 3H), 1.79(s, 3H),1.83(s, 3H), 1.99(s, 6H), 2.02(s, 3H), 2.12(s, 3H), 3.75(d, J=6.9Hz,2H), 3.80(br s, 1H), 4.89(d, J=6.9Hz, 2H), 5.39(t, J=6.9Hz, 1H), 5.59(t,J= 7.2Hz, 1H), 6.70(d, J=8.7Hz, 2H), 6.85(d, J=8.4Hz, 1H), 6.91-6.99(m,2H), 7.45(dd, J=2.4, 8.4Hz, 1H), 8.01(dd, J=0.9, 2.1Hz, 1H); IR (KBr):3395, 2970, 2911, 2855, 1613, 1603, 1519, 1376, 1277, 1185, 1126, 977,804 cm⁻¹ Ib-376 mp 187-188° C.; ¹H NMR (CDCl₃) δ 1.79(s, 3H), 1.83(s,3H), 1.99(s, 3H), 2.02(s, 3H), 2.12(s, 3H), 4.13(br s, 1H), 4.38(s, 2H),4.89(d, J=6.9Hz, 2H), 5.59(t, J=7.2Hz, 1H), 6.74(d, J=8.4Hz, 2H),6.85(d, J=8.4Hz, 1H), 6.93-6.96(m, 2H), 7.31-7.46(m, 6H), 8.01(d,J=1.8Hz, 1H); IR (KBr): 3358, 2964, 2929, 1613, 1526, 1490, 1451, 1280,1244, 1184, 1125, 997, 975, 804, 732 cm⁻¹ Ib-377 mp 75-76° C.; ¹H NMR(CDCl₃) δ 1.73(s, 3H), 1.77(s, 3H), 1.80(s, 3H), 1.83 (s, 3H), 2.01(s,3H), 2.07(s, 3H), 2.11(s, 3H), 3.37(s, 3H), 3.73(d, J= 6.6Hz, 2H),4.09(br s, 1H), 4.88(d, J=6.9Hz, 2H), 5.38(t, J=6.6Hz, 1H), 5.59(t,J=7.2Hz, 1H), 6.52-6.56(m, 2H), 6.84(d, J=7.5Hz, 1H), 6.85(s, 1H),6.96(d, J=7.8Hz, 1H), 7.59(dd, J=2.4, 8.4Hz, 1H), 8.14(d, J=1.8Hz, 1H);IR (KBr): 3424, 3339, 2969, 2927, 1611, 1509, 1460, 1353, 1282, 1252,1103, 984, 813 cm⁻¹

 

TABLE 128 Ib-378 mp 150-151° C.; ¹H NMR (CDCl₃) δ 1.80(s, 3H), 1.83(s,3H), 2.01(s, 3H), 2.06(s, 3H), 2.11(s, 3H), 3.37(s, 3H), 4.36(s, 2H),4.88(d, J=6.9Hz, 2H), 5.59(t, J=7.2Hz, 1H), 6.54-6.60(m, 2H), 6.84(d,J=8.4Hz, 1H), 6.84(s, 1H), 6.96(d, J=8.1Hz, 1H), 7.30-7.44(m, 5H),7.58(dd, J=2.4, 8.4Hz, 1H), 8.14(dd, J=0.9, 2.4Hz, 1H); IR (KBr): 3412,3272, 3018, 2927, 2858, 1611, 1517, 1459, 1375, 1355, 1317, 1283, 1243,1106, 1050, 985 cm⁻¹ Ib-379 mp 69-70° C.; ¹H NMR (CDCl₃) δ 1.74(s, 3H),1.78(s, 3H), 1.80(s, 3H), 1.83 (s, 3H), 2.13(s, 3H), 2.15(s, 3H),3.38(s, 3H), 3.72(d, J=6.9Hz, 2H), 4.88 (d, J=6.9Hz, 2H), 5.36(t,J=6.9Hz, 1H), 5.58(t, J=7.2Hz, 1H), 6.38-6.49 (m, 2H), 6.84(d, J=8.4Hz,1H), 6.95(s, 1H), 7.06(dd, J=8.1, 8.4Hz, 1H), 7.57(dd, J=2.4, 8.4Hz,1H), 8.13(d, J=1.8Hz, 1H); IR (KBr): 3416, 2972, 2930, 1627, 1522, 1462,1376, 1269, 1240, 1171, 1098, 963, 832 cm⁻¹ Ib-380 mp 156-157° C.; ¹HNMR (CDCl₃) δ 1.80(s, 3H), 1.83(s, 3H), 2.13(s, 3H), 2.14(s, 3H),3.38(s, 3H), 4.36(s, 2H), 4.89(d, J=7.2Hz, 2H), 5.58(t, J= 7.2Hz, 1H),6.40-6.51(m, 2H), 6.84(d, J=8.4Hz, 1H), 6.94(s, 1H), 7.09(dd, J=8.1,8.4Hz, 1H), 7.32-7.40(m, 5H), 7.58(dd, J=2.4, 8.4Hz, 1H), 8.13 (dd,J=0.6, 1.8Hz, 1H); IR (KBr): 3262, 3019, 2930, 1626, 1528, 1464, 1353,1317, 1284, 1244, 1170, 1105, 986, 821 cm⁻¹ Ib-381 mp 121-123° C.; ¹HNMR (CDCl₃) δ 1.74(s, 3H), 1.77(s, 3H), 1.80(s, 6H), 1.83(s, 3H),1.97(s, 3H), 2.00(s, 3H), 2.07(s, 3H), 3.51(s, 3H), 3.72(d, J= 6.9Hz,2H), 4.88(d, J=6.9Hz, 2H), 5.37(m, 1H), 5.58(m, 1H), 6.64(d, J= 8.7Hz,2H), 6.85(d, J=8.4Hz, 1H), 7.01-7.08(m, 2H), 7.38(dd, J=8.4, 2.4Hz, 1H),7.96(d, J=2.4Hz, 1H); IR (KBr) 3391, 1713, 1613, 1602, 1524, 1487, 1437,1298, 1276, 1243, 1222, 1122, 979 cm⁻¹ Ib-382 mp 126-128° C.; ¹H NMR(CDCl₃) δ 1.74(s, 3H), 1.77(s, 3H), 1.97(s, 3H), 2.00(s, 3H), 2.07(s,3H), 3.51(s, 3H), 3.72(d, J=6.6Hz, 2H), 5.37(m, 1H), 5.39(s, 2H),6.41(dd, J=3.0, 1.8Hz, 1H), 6.50(brd, J=3.0Hz, 1H), 6.64(d, J=8.7Hz,2H), 6.89(dd, J=8.4, 0.6Hz, 1H), 7.01-7.09(m, 2H), 7.40(dd, J= 8.4,2.4Hz, 1H), 7.48(dd, J=1.8, 0.6Hz, 1H), 7.98(dd, J=2.4, 0.6Hz, 1H); IR(KBr) 3384, 1714, 1612, 1523, 1490, 1343, 1322, 1301, 1281, 1246, 1224,1124, 990 cm⁻¹ Ib-383 mp 161-163° C.; ¹H NMR (CDCl₃) δ 1.73(s, 3H),1.77(s, 3H), 1.91(t, J= 2.4Hz, 3H), 1.96(s, 3H), 1.99(s, 3H), 2.07(s,3H), 3.51(s, 3H), 3.72(d, J= 6.6Hz, 2H), 5.01(q, J=2.4Hz, 2H), 5.37(m,1H), 6.65(d, J=9.0Hz, 2H), 6.90(dd, J=8.7, 0.9Hz, 1H), 7.01-7.08(m, 2H),7.40(dd, J=8.7, 2.4Hz, 1H), 7.97(dd, J=2.4, 0.9Hz, 1H); IR (KBr) 3385,1725, 1613, 1603, 1525, 1488, 1344, 1329, 1303, 1281, 1246, 1221, 999cm⁻¹ Ib-384 Oil ¹H NMR (CDCl₃) δ 1.78(s, 3H), 1.82(s, 3H), 2.30(s, 3H),2.44(s, 3H), 4.64(d, J=6.6Hz, 2H), 5.55(m, 1H), 6.99-7.12(m, 3H),7.17(s, 1H), 7.37(s, 1H), 7.53(d, J=1.2Hz, 1H), 9.07(d, J=1.2Hz, 1H)Ib-385 mp 93-94° C.; ¹H NMR (CDCl₃) δ 1.77(s, 3H), 1.81(s, 3H), 2.28(s,3H), 2.40 (s, 3H), 4.05(s, 3H), 4.64(d, J=6.9Hz, 2H), 5.55(m, 1H),6.86(d, J= 1.2Hz, 1H), 6.98-7.12(m, 3H), 7.26(s, 1H), 7.34(s, 1H),8.87(d, J=1.2Hz, 1H); IR (KBr) 1589, 1533, 1518, 1496, 1394, 1364, 1299,1263, 1232, 1123, 1040, 997, 986, 872 cm⁻¹

 

TABLE 129 Ib-386 mp 95-96° C.; ¹H NMR (CDCl₃) δ 1.77(s, 3H), 1.81(s,3H), 2.28(s, 3H), 2.38 (s, 3H), 3.17(s, 6H), 4.64(d, J=6.9Hz, 2H),5.55(m, 1H), 6.53(d, J= 1.2Hz, 1H), 6.98-7.14(m, 4H), 7.29(s, 1H),8.69(d, J=1.2Hz, 1H); IR (KBr) 1591, 1512, 1417, 1405, 1299, 1278, 1261,1228, 1123, 1000, 836, 827 cm⁻¹ Ib-387 mp 88-90° C.; ¹H NMR (CDCl₃) δ1.78(s, 3H), 1.83(s, 3H), 2.29(s, 3H), 2.30 (s, 3H), 4.57(d, J=6.6Hz,2H), 5.55(t, J=6.6Hz, 1H), 6.99(d, J=8.4Hz, 2H), 7.12(s, 1H), 7.20(s,1H), 7.28(d, J=8.4Hz, 2H), 8.79(s, 2H), 9.22(s, 1H); IR (KBr) 1611,1519, 1497, 1415, 1384, 1240, 1007, 820, 731 cm⁻¹. Ib-388 mp 97-98° C.;¹H NMR (CDCl₃) δ 1.78(s, 3H), 1.82(s, 3H), 2.29(s, 3H), 2.30 (s, 3H),4.64(d, J=6.6Hz, 2H), 5.55(t, J=6.6Hz, 1H), 7.00-7.14(m, 4H), 7.18(s,1H), 8.78(s, 2H), 9.22(s 1H); IR (KBr) 1523, 1502, 1415, 1386, 1313,1285, 1274, 1263, 1233, 1200, 1131, 995, 858 cm⁻¹. Ib-389 mp 163-166°C.; ¹H NMR (CDCl₃) δ 1.77(s, 3H), 1.82(s, 3H), 2.29(s, 3H), 4.56(d,J=6.6Hz, 2H), 5.11(tm, J=6.6Hz, 1H), 6.98(d, J=8.7Hz, 2H), 7.08(s, 1H),7.16(s, 1H), 7.27(d, J=8.7Hz, 2H), 8.35(s, 2H); IR (KBr) 3393, 3315,3196, 1639, 1605, 1595, 1518, 1480, 1236, 1002, 838, 802 cm⁻¹. Ib-390 mp158-160° C.; ¹H NMR (CDCl₃) δ 1.77(s, 3H), 1.82(s, 3H), 2.28(s, 3H),2.29(s, 3H), 4.64(d, J=6.6Hz, 2H), 5.17(s, 2H), 5.56(t, J=6.6Hz, 1H),6.98-7.16(m, 5H), 8.35(s, 2H); IR (KBr) 3334, 3187, 1655, 1598, 1522,1486, 1296, 1269, 1230, 1125, 998 cm⁻¹. Ib-391 mp 156-158° C.; ¹H NMR(CDCl₃) δ 1.75(s, 3H), 1.77(s, 6H), 1.82(s, 3H), 2.28(s, 3H), 2.30(s,3H), 4.05(t, J=6.0Hz, 2H), 4.56(d, J=6.6Hz, 2H), 5.11(t, J=5.4Hz, 1H),5.36(tm, J=6.6Hz, 1H), 5.54(t, J=6.6Hz, 1H), 6.97(d, J=9.0Hz, 2H),7.08(s, 1H), 7.15(s, 1H), 7.27(d, J=9.0Hz, 2H), 8.34(s, 2H); IR (KBr)3236, 1608, 1598, 1522, 1495, 1436, 1264, 1244, 1181, 998, 833, 803cm⁻¹. Ib-392 mp 105-106° C.; ¹H NMR (CDCl₃) δ 1.75(s, 3H), 1.77(s, 6H),1.82(s, 3H), 2.28(s, 3H), 2.30(s, 3H), 4.00-4.09(m, 2H), 4.63(d,J=6.6Hz, 2H), 5.14(m, 1H), 5.37(m, 1H), 5.55(t, J=6.6Hz, 1H),6.98-7.17(m 5H), 8.34(s, 2H); IR (KBr) 3254, 1607, 1524, 1495, 1440,1300, 1271, 1235, 1129, 995 cm⁻¹. Ib-393 mp 182-184° C.; ¹H NMR (CDCl₃)δ 1.74(s, 3H), 1.77(s, 3H), 2.29(s, 6H), 4.05(dd, J=6.6, 5.7Hz, 2H),5.17(brs, 1H), 5.37(tm, J=6.6Hz, 1H), 6.75 (d, J=8.7Hz, 2H), 7.07(s,1H), 7.14(s, 1H), 7.15(d, J=8.7Hz, 2H), 8.34(s, 2H); IR (KBr) 3443,3327, 3245, 3110, 1631, 1602, 1525, 1493, 1440, 1301, 828, 802 cm⁻¹Ib-394 mp 160-162° C.; ¹H NMR (CDCl₃) δ 1.74(s, 6H), 1.77(s, 6H),2.29(s, 3H), 2.30(s, 3H), 3.74(d, J=6.9Hz, 2H), 4.05(dd, J=6.6, 6.0Hz,2H), 5.15(brs, 1H), 5.37(m, 2H), 6.67(d, J=8.4Hz, 2H), 7.07(s, 1H),7.16(s, 1H), 7.18(d, J=8.4Hz, 2H), 8.34(s, 2H); IR (KBr) 3423, 3240,3104, 1612, 1598, 1525, 1496, 1436, 1321, 1262, 1187, 1087, 824, 802cm⁻¹ Ib-395 mp 106-108° C.; ¹H NMR (CDCl₃) δ 1.72(s, 6H), 1.74(s, 9H),1.77(s, 3H), 2.29(s, 3H), 2.32(s, 3H), 3.91(d, J=5.7Hz, 4H), 4.04(dd,J=6.3, 5.7Hz, 2H), 5.08(m, 1H), 5.27(m, 2H), 5.37(m, 1H), 6.72(brd,J=8.7Hz, 2H), 7.07(s, 1H), 7.17(s, 1H), 7.21(d, J=8.7Hz, 2H), 8.34(s,2H); IR (KBr) 3433, 3254, 3110, 1599, 1523, 1494, 1434, 1378, 1232,1196, 1092, 817, 801 cm⁻¹

 

TABLE 130 Ib-396 mp 84-86° C.; ¹H NMR (CDCl₃) δ 1.74(s, 3H), 1.77(s,3H), 1.79(s, 3H), 2.23 (s, 3H), 2.28(s, 3H), 3.71(d, J=6.9Hz, 2H),4.93(d, J 6.9Hz, 2H), 5.32- 5.61(m, 2H), 6.36-6.48(m, 2H), 7.05(t,J=8.4Hz, 1H), 7.09(s, 1H), 7.15(s, 1H), 8.53(s, 2H) IR (KBr): 3224,3315, 2970, 2923, 1628, 1592, 1534, 1474, 1438, 1377, 1341, 1317, 1249,1173, 1110, 993 cm⁻¹ Ib-397 mp 150-152° C.; ¹H NMR (CDCl₃) δ 1.74(s,3H), 1.78(s, 3H), 1.80(s, 3H), 1.81(s, 3H), 1.99(s, 6H), 2.00(s, 6H),3.74(d, J=6.9Hz, 2H), 4.95(d, J= 7.2Hz, 2H), 5.37-5.42(m, 1H),5.58-5.64(m, 1H), 6.68-6.71(m, 2H), 6.93- 6.97(m, 2H), 8.36(s, 2H) IR(KBr): 3360, 2973, 2928, 2857, 1610, 1587, 1519, 1436, 1406, 1379, 1310,1245, 1181, 983 cm⁻¹ Ib-398 mp 156-158° C.; ¹H NMR (CDCl₃) δ 1.60(s,3H), 1.75(s, 3H), 1.77(s, 3H), 1.82(s, 3H), 1.97(s, 6H), 2.03(s, 6H),4.04-4.08(m, 2H), 4.64(d, J=6.6Hz, 2H), 5.05-5.08(m, 1H), 5.30-5.41(m,1H), 5.54-5.60(m, 1H), 6.81-6.84(m, 1H), 6.89(dd, J=1.8, 12.0Hz, 1H),7.05(t, J=8.7Hz, 1H), 8.15(s, 1H), IR (KBr): 3320, 2971, 2931, 2850,1627, 1604, 1525, 1483, 1395, 1373, 1338, 1309, 1288, 1263, 1240, 1175,1115, 1038 cm⁻¹. Ib-399 mp 161-163° C.; ¹H NMR (CDCl₃) δ 1.77(s, 3H),1.82(s, 3H), 1.97(s, 6H), 2.02(s, 6H), 4.64(d, J=6.6Hz, 2H), 5.13(br s,2H), 5.54-5.60(m, 1H), 6.80-6.84(m, 1H), 6.88(dd, J=1.8, 11.7Hz, 1H),7.05(t, J=8.7Hz, 1H), 8.16(s, 1H) IR (KBr): 3344, 3210, 2987, 2917,2859, 1654, 1618, 1597, 1541, 1513, 1479, 1427, 1382, 1295, 1263, 1240,1212, 1114, 993 cm⁻¹. Ib-400 ¹H NMR (300 MHz, CDCl₃) δ 1.75(s, 3H),1.77(s, 6H), 1.82(s, 3H), 2.05(s, 3H), 2.12(s, 3H), 3.34(s, 3H), 3.39(s,3H), 4.06(t, J=6.0Hz, 2H), 4.65(d, J=6.9Hz, 2H), 5.18(t, J=5.3Hz, 1H),5.35-5.42(m, 1H), 5.53-5.60(m, 1H), 7.08-6.95(m, 3H), 8.30(s, 2H).Ib-401 Oil; ¹H NMR (CDCl₃) δ 1.77(s, 3H), 1.82(s, 3H), 2.31(s, 3H),2.54(s, 3H), 4.56(d, J=6.6Hz, 2H), 5.54(t, J=6.6Hz, 1H), 6.98(d,J=8.4Hz, 2H), 7.16 (s, 1H), 7.21(t, J=5.1Hz, 1H), 7.28(d, J=8.4Hz, 2H),7.73(s, 1H), 8.85(d, J=5.1Hz, 2H). Ib-402 mp 93-94° C.; ¹H NMR (CDCl₃) δ1.77(s, 3H), 1.82(s, 3H), 2.31(s, 3H), 2.54 (s, 3H), 4.64(d, J=6.6Hz,2H), 5.55(t, J=6.6Hz, 1H), 6.98-7.25(m, 5H), 7.73(s, 1H), 8.85(s, 1H),8.86(s 1H); IR (KBr) 1573, 1560, 1521, 1414, 1299, 1277, 1260, 1238,1130, 997 cm⁻¹. Ib-403 mp 107-108° C.; ¹H NMR (CDCl₃) δ 1.74(s, 3H),1.77(s, 3H), 1.81(s, 3H), 1.83(s, 3H), 2.32(s, 3H), 2.39(s, 3H), 3.67(brs, 1H), 3.74(d, J=6.8Hz, 2H), 5.10(d, J=7.1Hz, 2H), 5.37(br t, J=6.8Hz,1H), 5.62(br t, J=7.1 Hz, 1H), 6.67(d, J=8.5Hz, 2H), 7.02(d, J=9.0Hz,1H), 7.17(s, 1H), 7.20 (d, J=8.5Hz, 2H), 7.33(s, 1H), 7.52(d, J=9.0Hz,1H) Ib-404 mp 149-151° C.: ¹H NMR (CDCl₃) δ 1.78(s, 6H), 1.82(s, 3H),2.31(s, 3H), 2.38(s, 3H), 4.57(d, J=6.6Hz, 2H), 5.54(t, J=6.6Hz, 1H),6.99(d, J= 9.0Hz, 2H), 7.20(s, 1H), 7.27(d, J=9.0Hz, 2H), 7.34(s, 1H),7.58(d, J= 9.0Hz, 1H), 7.60(d, J=9.0Hz, 1H); IR (KBr) 1610, 1572, 1517,1496, 1421, 1411, 1249, 1179, 1142, 1012, 1004, 857, 841 cm⁻¹.

 

TABLE 131 Ib-405 mp 94-94.5° C.; ¹H NMR (CDCl₃) δ 1.77 (s, 3H), 1.82 (s,3H), 2.30 (s, 3H), 2.39(s, 3H), 4.20(s, 3H), 4.57(d, J=6.6 Hz, 2H),5.54(tm, J=6.6 Hz, 1H), 6.98(d, J=8.7 Hz, 2H), 7.04(d, J=9.0 Hz, 1H),7.18(s, 1H), 7.28(d, J= 8.7 Hz, 2H), 7.34(s, 1H), 7.53(d, J=9.0 Hz, 1H); IR (KBr) 1610, 1592, 1518, 1464, 1415, 1295, 1235, 1175, 1107, 1016,867, 830 cm⁻¹. Ib-406 mp 165-167° C.; ¹H NMR (CDCl₃) δ 1.77(s, 3H),1.82(s, 3H), 2.29(s, 3H), 2.41(s, 3H), 3.24(s. 6H), 4.56(d, J=6.6 Hz,2H), 5.54(tm, J=6.6 Hz, 1H), 6.87(d, J=9.3 Hz. 1H), 6.97(d, J=9.0 Hz,2H), 7.15(s, 1H), 7.28(d, J= 9.0 Hz, 2H), 7.36(s, 1H), 7.38(d, J=9.3 Hz,1H) ; IR (KBr) 1606, 1593, 1493, 1427, 1387, 1237, 1178, 1003, 847, 826cm⁻¹. Ib-407 mp 138-140° C.; ¹H NMR (CDCl₃) δ 1.78(s, 3H), 1.82(s, 3H),2.30(s, 3H), 2.38(s, 3H), 4.64(d, J=6.6 Hz, 2H), 5.55(t, J=6.6 Hz, 1H),7.00-7.13(m, 3H), 7.19(s, 1H), 7.34(s, 1H), 7.56(m, 1H) 7.62(m, 1H) ; IR(KBr) 1518, 1496, 1414, 1385, 1299, 1266, 1233, 1127, 994, 851 cm⁻¹.Ib-408 mp 91-92° C.; ¹H NMR (CDCl₃) δ 1.77(s, 3H), 1.82(s, 3H), 2.29(s,3H), 2.39 (s, 3H), 4.20(s, 3H), 4.64(d, J=6.6 Hz, 2H), 5.55(t, J=6.6 Hz,1H), 6.90- 7.14(m, 4H), 7.16(s, 1H), 7.34(s, 1H), 7.53(d, J=9.0 Hz, 1H); IR (KBr) 1593, 1519, 1496, 1469, 1417, 1294, 1274, 1263, 1231, 1126,1010, 995, 845 cm⁻¹. Ib-409 mp 132-134° C.; ¹H NMR (CDCl₃) δ 1.77(s,3H), 1.82(s, 3H), 2.29(s, 3H), 2.41(s, 3H), 3.24(s, 6H), 4.64(d, J=6.6Hz, 2H), 5.55(t, J=6.6 Hz, 1H), 6.87(d, J=9.6 Hz, 1H), 6.97-7.15(m, 4H),7.36(s, 1H), 7.37(d, J=9.6 Hz, 1H); IR (KBr) 1597, 1547, 1519, 1495,1422, 1404, 1297, 1272, 1233, 1197, 1133, 993, 849 cm⁻¹. Ib-410 mp197-200° C.; ¹H NMR (CDCl₃) δ 1.77(s, 3H), 1.82(s, 3H), 2.29(s, 3H),2.36(s, 3H), 4.56(d, J=6.9 Hz, 2H), 4.82(s, 2H), 5.54(tm, J=6.9 Hz, 1H),6.83(d, J=9.0 Hz, 1H), 6.97(d, J=9.0 Hz, 2H), 7.16(s, 1H), 7.27(d, J=9.0 Hz, 2H), 7.31(s, 1H), 7.39(d, J=9.0 Hz, 1H) ; IR (KBr) 3486, 3370,3308, 3164, 1649, 1625, 1606, 1516, 1495, 1461, 1234, 1216, 1173, 1011,999, 982, 846, 835 cm⁻¹. Ib-411 mp 183-185° C.; ¹H NMR (CDCl₃) δ 1.77(s,3H), 1.82(s, 3H), 2.28(s, 3H), 2.36(s, 3H), 4.64(d, J=6.6 Hz, 2H),4.89(brs, 2H), 5.55(tm, J=6.6 Hz, 1H), 6.85(d, J=9.0 Hz, 1H),6.98-7.12(m, 3H), 7.14(s, 1H), 7.32(s, 1H), 7.38(d, J=9.0 Hz, 1H) ; IR(KBr) 3486, 3368, 3308, 3161, 1649, 1624, 1519, 1497, 1461, 1261, 1123,982, 844 cm⁻¹. Ib-412 mp 138-140° C.; ¹H NMR (CDCl₃) δ 1.76(s, 6H),1.77(s, 3H), 1.82(s, 3H), 2.29(s, 3H), 2.39(s, 3H), 4.03(t, J=6.3 Hz,2H), 4.56(d, J=6.9 Hz, 2H), 4.77(m, 1H), 5.38(tm, J=6.9 Hz, 1H),5.54(tm, J=6.9 Hz, 1H), 6.70(d, J= 9.0 Hz, 1H), 6.97(d, J=9.0 Hz, 2H),7.15(s, 1H), 7.28(d, J=9.0 Hz, 2H), 7.33(s, 1H), 7.35(d, J=9.0 Hz, 1H) ;IR (KBr) 3213, 1605, 1530, 1492, 1234, 1180, 994, 841 cm⁻¹. Ib-413 mp113-115° C.; ¹H NMR (CDCl₃) δ 1.76(s, 3H), 1.77(s, 3H), 1.78(s, 3H),1.81(s, 3H), 2.28(s, 3H), 2.39(s, 3H), 3.98-4.15(m, 2H), 4.64(d, J=6.9Hz, 2H), 4.76(m, 1H), 5.38(m, 1H), 5.55(tm, J=6.9 Hz, 1H), 6.70(d J=9.3Hz, 1H). 6.98-7.15(m, 4H), 7.33(s, 1H), 7.35(d, J=9.3 Hz, 1H) ; IR (KBr)3424, 3214, 1601, 1534, 1492, 1416, 1296, 1261, 1232, 1126, 983, 829cm⁻¹.

 

TABLE 132 Ib-414 mp 159-161° C.; ¹H NMR (CDCl₃) δ 1.76(s, 3H), 1.78(s,3H), 2.29(s, 3H), 2.38(s, 3H), 4.03(dd, J=6.6, 5.7 Hz, 2H), 4.91(m, 1H),5.38(tm, J=6.6 Hz, 1H), 6.71(d, J=9.0 Hz, 2H), 6.75(d, J=8.7 Hz, 2H),7.15(s, 1H), 7.17(d, J=8.7 Hz, 2H), 7.32(s, 1H), 7.37(d, J=9.0 Hz, 1H) ;IR (KBr) 3440, 3363, 3220, 1621, 1599, 1531, 1491, 1458, 1410, 1279,1181, 1140, 1045, 1026, 835 cm⁻¹ Ib-415 mp 131-133° C.; ¹H NMR (CDCl₃) δ1.74(s, 3H), 1.76(s, 3H), 1.77(s, 6H), 2.31(s, 3H), 2.38(s, 3H), 3.74(d,J=6.9 Hz, 2H), 4.03(dd, J=6.0, 6.0 Hz, 2H), 4.87(brs, 1H), 5.38(m, 2H),6.67(d, J=8.4 Hz, 2H), 6.71(d, J=9.3 Hz, 1H), 7.15(s, 1H), 7.19(d, J=8.4Hz, 2H), 7.32(s, 1H), 7.36(d, J=9.3 Hz, 1H) ; IR (KBr) 3385, 3207, 1609,1529, 1493, 1457, 1186, 1045, 834 cm⁻¹ Ib-416 mp 174-175° C.; ¹H NMR(CDCl₃) δ 1.72(s, 6H), 1.74(s, 3H), 1.75(s, 3H), 1.76(s, 3H), 1.78(s,3H), 2.33(s, 3), 2.38(s, 3H), 3.91(d, J=6.0 Hz, 4H), 4.03(dd, J=6.0, 6.0Hz, 2H), 4.88(m, 1H), 5.26(m, 2H), 5.38(m, 1H), 6.71 (d, J=9.0 Hz, 1H),6.75(d, J=9.0 Hz, 2H), 7.17(s, 1H), 7.22(d, J=9.0 Hz, 2H), 7.32(s, 1H),7.37(d, J=9.0 Hz, 1H); IR (KBr) 3432, 3252, 3133, 1615, 1578, 1524,1473, 1449, 1350, 1316, 1305, 1234, 1195, 1162, 1057, 854, 819 cm⁻¹.Ib-417 mp 224-227° C.; ¹H NMR (CDCl₃) δ 1.77(s, 3H); 1.82(s, 3H);1.95(s, 6H); 1.96(s, 6H); 4.64(d, J=6.6 Hz, 2H); 4.91(br s, 2H); 5.57(m,1H); 6.75-7.07 (m, 4H) 7.20(dd, J=1.8, 9.0 Hz, 1H); IR (KBr): 3341,3163, 1637, 1513, 1460, 1297, 1263, 1243, 1114, 1001 cm⁻¹. Ib-418 mp215-216° C.; ¹H NMR (CDCl₃) δ 1.77(s, 6H); 1.79(s, 3H); 1.82(s, 3H);1.95(s, 6H); 1.97(s, 6H); 4.02(t, J=6.3 Hz, 2H); 4.64(d, J=7.2 Hz, 2H);4.84(br, 1H); 5.39(m, 1H); 5.57(m, 1H); 6.74(dd, J=1.2, 9.0 Hz, 1H);6.76-6.93(m, 2H); 7.04(t, J=8.4 Hz, 1H); 7.15(dd, J=1.8, 9.0 Hz, 1H); IR(KBr): 3258, 2917, 1609, 1513, 1486, 1466, 1426, 1297, 1264, 1241, 1118cm⁻¹. Ib-419 mp 178-180° C.; ¹H NMR (CDCl₃) δ 1.74(s, 3H), 1.78(s, 3H),1.82(s, 3H), 1.85(s, 3H), 1.95(s, 6H), 1.98(s, 6H), 3.4(br s, 1H),3.75(d, J=6.9 Hz, 2H), 5.11(d, J=6.9 Hz, 2H), 5.40(t, J=6.9 Hz, 1H),5.63(d, J=6.9 Hz, 1H), 6.70-6.74(m, 2H), 6.92-6.99(m, 2H), 7.04(d, J=9.2Hz, 1H), 7.32(d, J= 9.2 Hz, 1H) ; IR (KBr): 3368, 2979, 2932, 2915,1612, 1520, 1438, 1303, 1285, 966, 821, 529 cm⁻¹. Ib-420 ¹H NMR (300MHz, CDCl₃) δ 1.77(s, 6H), 1.79(d, J=1.2 Hz, 3H), 1.82(d, J=0.9 Hz, 3H),2.04(s, 3H), 2.12(s, 3H), 3.35(s, 3H), 3.42(s, 3H), 4.02(t, J=6.2 Hz,2H), 4.65(d, J=6.9 Hz, 2H), 4.81(t, J=5.0 Hz, 1H), 5.35-5.42(m, 1H),5.53-5.60(m, 1H), 6.72(d, J=9.2 Hz, 1H), 6.95-7.08(m, 3H), 7.29(d, J=9.2Hz, 1H). Ib-421 mp 88-89° C.: ¹H NMR (CDCl₃) δ 1.78(s, 3H), 1.82(s, 3H),2.31(s, 3H), 2.40 (s, 3H), 4.57(d, J=6.6 Hz, 2H), 5.54(t, J=6.6 Hz, 1H),6.98(d, J=9.0 Hz, 2H), 7.19(s, 1H), 7.28(d, J=9.0 Hz, 2H), 7.35(s, 1H),8.53(d, J=2.7 Hz, 1H), 8.68(dd, J=2.7, 1.2 Hz, 1H), 8.78(d, J=1.2 Hz,1H) ; IR (KBr) 1606, 1574, 1516, 1496, 1469, 1386, 1241, 1178, 1145,1011, 1002, 982, 840, 833 cm⁻¹. Ib-422 mp 87-88° C.; ¹H NMR (CDCl₃) δ1.77(s, 3H), 1.82(s, 3H), 2.31(s, 3H), 2.40 (s, 3H), 4.64(d, J=6.6 Hz,2H), 5.55(t, J=6.6 Hz, 1H), 6.99-7.14(m 3H), 7.17(s, 1H), 7.35(s, 1H),8.54(m, 1H), 8.68(m, 1H), 8.77(m, 1H) ; IR (KBr) 1517, 1501, 1476, 1447,1397, 1387, 1315, 1297, 1265, 1234, 1198, 1127, 996, 849 cm⁻¹.

 

TABLE 133 Ib-423 mp 74-77° C.; ¹H NMR (CDCl₃) δ 1.77(s, 3H), 1.82(s,3H), 2.29(s, 3H), 2.37 (s, 3H), 4.56(d, J=6.9 Hz, 2H), 4.60(s, 2H),5.54(tm, J=6.9 Hz, 1H), 6.97 (d, J=8.7 Hz, 2H), 7.14(s, 1H), 7.27(d,J=8.7 Hz, 2H), 7.29(s, 1H), 8.10(s, 1H), 8.18(s 1H); IR (KBr) 3464,3319, 3165, 1606, 1477, 1381, 1241, 1178, 1023, 1002, 839, 832 cm⁻¹.Ib-424 mp 127-128° C.; ¹H NMR (CDCl₃) δ 1.77(s, 3H), 1.81(s, 3H),2.28(s, 3H), 2.37(s, 3H), 4.62(s, 2H), 4.63(d, J=6.6 Hz, 2H), 5.55(t,J=6.6 Hz, 1H), 6.98-7.12(m, 3H), 7.13(s, 1H), 7.29(s 1H), 8.09(d, J=1.5Hz, 1H), 8.17(d, J=1.5 Hz, 1H) ; IR (KBr) 3426, 3306, 3189, 1641, 1580,1536, 1517, 1498, 1482, 1393, 1292, 1281, 1265, 1231, 1121, 982 cm⁻¹.Ib-425 mp 136-138° C.; ¹H NMR (CDCl₃) δ 1.77(s, 3H), 1.82(s, 3H),2.28(s, 3H), 2.38(s, 3H), 3.74(m, 1H), 4.56(d, J=6.9 Hz, 2H), 5.54(tm,J=6.9 Hz, 1H), 6.97(d, J=8.7 Hz, 2H), 7.13(s, 1H), 7.27(d, J=8.7 Hz,2H), 7.29(s, 1H), 7.96(d, J=1.2 Hz, 2H), 8.16(d, J=1.2 Hz, 1H) ; IR(KBr) 3282, 1597, 1527, 1492, 1241, 1174, 1018, 885, 826 cm⁻¹. Ib-426 mp119-121° C.; ¹H NMR (CDCl₃) δ 1.77(s, 3H), 1.81(s, 3H), 2.28(s, 3H),2.38(s, 3H), 3.74(m, 1H), 4.57(d, J=8.1 Hz, 1H), 4.63(d, J=6.6 Hz, 2H),5.55(t, J=6.6 Hz, 1H), 6.98-7.12(m, 3H), 7.11(s, 1H), 7.29(s, 1H),7.96(d, J=1.5 Hz, 1H), 8.15(d, J=1.5 Hz, 1H) ; IR (KBr) 3424, 3275,1598, 1528, 1495, 1280, 1265, 1173, 1018, 1007 cm⁻¹. Ib-427 mp 134-136°C.; ¹H NMR (CDCl₃) δ 1.77(s, 3H), 1.78(s, 6H), 1.82(s, 3H), 2.29(s, 3H),2.38(s, 3H), 3.98(t, J=5.4 Hz, 2H), 4.56(d, J=6.9 Hz, 2H), 5.36(tm,J=6.9 Hz, 1H), 5.54(tm, J=6.9 Hz, 1H), 6.97(d, J=8.7 Hz, 2H), 7.14(s,1H), 7.27(d, J=8.7 Hz, 2H), 7.29(s, 1H), 7.98(d, J=1.5 Hz, 1H),8.19(d,J=1.5 Hz, 1H) ; IR (KBr) 3215, 1608, 1578, 1561, 1492, 1380,1362, 1243, 1179, 1166, 1017, 1003, 830 cm⁻¹. Ib-428 mp 99-100° C.; ¹HNMR (CDCl₃) δ 1.76(s, 6H), 1.78(s, 3H), 1.81(s, 3H), 2.28 (s, 3H),2.38(s, 3H), 3.98(dd, J=6.6, 5.4 Hz, 2H), 4.59 (brs, 1H), 4.63(d, J= 6.6Hz, 2H), 5.36(t, J=6.6 Hz, 1H), 5.55(t, J=6.6 Hz, 1H), 6.98-7.12(m, 3H),7.12(s, 1H), 7.30(s, 1H), 7.98(d, J=1.5 Hz, 1H), 8.18(d, J=1.5 Hz, 1H) ;IR (KBr) 3239, 1578, 1565, 1492, 1390, 1362, 1303, 1277, 1261, 1122,995, 873, 827 cm⁻¹ Ib-429 mp 133-134° C.; ¹H NMR (CDCl₃) δ 1.74(s, 3H),1.76(s, 3H), 1.77(s, 3H), 1.78(s, 3H), 2.31(s, 3H), 2.38(s, 3H), 3.73(d,J=6.6 Hz, 2H), 3.97(dd, J= 6.0, 6.0 Hz, 2H), 4.57(m, 1H), 5.37(m, 2H),6.67(d, J=8.4 Hz, 2H), 7.14(s, 1H), 7.19(d, J=8.4 Hz, 2H), 7.28(s, 1H),7.97(d, J=1.5 Hz, 1H), 8.19(d, J=1.5 Hz, 1H) ; IR (KBr) 3413, 3222,1612, 1580, 1561, 1523, 1493, 1457, 1379, 1362, 1319, 1186, 1165, 1094,1056, 1017, 822 cm⁻¹ Ib-430 Oil ¹H NMR (CDCl₃) δ 1.72(s, 6H), 1.74(s,6H), 1.76(s, 3H), 1.78(s, 3H), 2.33(s, 3H), 2.37(s, 3H), 3.90(d, J=6.3Hz, 4H), 3.97(dd, J=6.0, 5.1 Hz, 2H), 4.54(m, 1H), 5.26(m, 2H), 5.36(m,1H), 6.74(d, J=8.7 Hz, 2H), 7.15 (s, 1H), 7.21(d, J=8.7 Hz, 2H), 7.15(s,1H), 7.21(d, J=8.7 Hz, 2H), 7.28(s, 1H), 7.98(d, J=1.5 Hz, 1H) 8.19(d,J=1.5 Hz, 1H)

 

TABLE 134 Ib-431 mp 167-168° C.; ¹H NMR (CDCl₃) δ 1.75(s, 3H), 1.78(s,3H), 1.81(s, 3H), 1.84(s, 3H), 1.95(s, 6H), 1.98(s, 6H), 3.63 (br s,1H), 3.74(d, J=6.6 Hz, 2H), 4.90(d, J=7.1 Hz, 2H), 5.39(t, J=6.6 Hz,1H), 5.58(d, J=7.1 Hz, 1H), 6.67-6.71(m, 2H), 6.87-7.00(m, 2H), 8.07(d,J=1.5 Hz, 1H), 8.35(d, J= 1.5 Hz, 1H); IR (KBr): 3355, 2964, 2926, 2874,1614, 1521, 1458, 1345, 1312, 1270, 1029, 977, 820 cm⁻¹. Ib-432 mp161-162° C.; ¹H NMR (CDCl₃) δ 1.77(s, 3H); 1.82(s, 3H); 1.94(s, 6H);1.97(s, 6H); 4.64(d, J=6.3 Hz, 2H); 4.64(br s, 2H); 5.57(m, 1H);6.74-7.07 (m, 3H); 7.98(s, 1H); 8.15(s, 1H); IR (KBr): 3450, 3340, 2921,1624, 1527, 1514, 1461, 1374, 1295, 1261, 1245, 1192, 1116 cm⁻¹. Ib-433mp 130-132° C.; ¹H NMR (CDCl₃) δ 1.77(s, 6H); 1.80(s, 3H); 1.82(s, 3H);1.94(s, 6H); 1.98(s, 6H); 3.98 (br t, J=5.4 Hz, 2H); 4.56(br, 1H);4.64(d, J=6.6 Hz, 2H); 5.39(m, 1H); 5.57(m, 1H); 6.74-7.08(m, 3H);7.99(s, 1H); 8.02(s, 1H); IR (KBr): 3244, 2918, 1584, 1560, 1514, 1468,1380, 1295, 1264, 1241, 1114 cm⁻¹. Ib-434 amorphous; ¹H NMR (CDCl₃) δ1.77(s, 3H), 1.80(s, 3H), 1.96(s, 6H), 1.98(s, 6H), 3.5(br s, 2H),3.98(m, 2H), 4.64(m, 1H), 5.39(m, 1H), 6.74- 6.79(m, 2H), 6.84-6.99(m,2H), 7.99(d, J=1.4 Hz, 1H), 8.04(d, J=1.4 Hz, 1H); IR (KBr): 3334, 1620,1588, 1519, 1462, 1276, 1161, 1024, 824, 525 cm⁻¹ Ib-435 mp 180-182° C.;¹H NMR (CDCl₃) δ 1.74(s, 3H), 1.74(s, 3H), 1.78(s, 3H), 1.79(s, 3H),1.97(s, 6H), 1.98(s, 6H), 3.4(br s, 1H), 3.74(d, J=6.9 Hz, 2H), 3.98(t,J=6.0 Hz, 2H), 4.50(t, J=5.1 Hz, 1H), 5.36-5.41(m, 2H), 6.66-6.72(m,2H), 6.86-7.02(m, 2H), 8.00(d, J=1.4 Hz, 1H), 8.02(d, J= 1.4 Hz, 1H); IR(CHCl₃): 3439, 1613, 1585, 1519, 1468 cm⁻¹ Ib-436 ¹H NMR (300 M Hz,CDCl₃) δ 1.77(s, 6H), 1.79(d, J=0.9 Hz, 3H), 1.81(s, 3H), 2.04(s, 3H),2.08(s, 3H), 3.34(s, 3H), 3.41(s, 3H), 3.99(t, J=5.3 Hz, 2H), 4.64(d,J=6.9 Hz, 2H), 4.58-4.67(m, 1H), 5.34-5.42(m, 1H), 5.53-5.60 (m, 1H),6.93-7.07(m, 3H), 8.02(d, J=1.5 Hz, 1H), 8.11(d, J=1.5 Hz, 1H). Ib-437foam; ¹H NMR (CDCl₃) δ 2.21(s, 3H), 2.28(s, 3H), 6.34-6.49(m, 2H), 6.80(d, J=2.1 Hz, 1H), 7.03-7.12(m, 3H), 7.40(d, J=2.4 Hz, 1H), 7.61(m, 1H)IR (KBr): 3414, 2862, 2589, 1652, 1601, 1541, 1492, 1430, 1330, 1186,1222, 1186, 1147, 1123, 1040, 998 cm⁻¹ Ib-438 foam; ¹H NMR (CDCl₃) δ2.12(s, 3H), 2.78(s, 3H), 6.61-6.81(m, 3H), 6.99-7.06(m, 3H), 7.41(d,J=2.1 Hz, 1H), 7.58(dd, J=2.4, 8.7 Hz, 1H) IR (KBr): 3423, 2857, 2604,1654, 1602, 1539, 1447, 1413, 1215, 1133, 1074 cm⁻¹ Ib-439 foam; ¹H NMR(CDCl₃) δ 1.73(s, 3H), 1.79(s, 3H), 2.14(s, 3H), 2.28(s, 3H), 3.71(d,J=6.6 Hz, 2H), 5.33-5.39(m, 1H), 6.65-6.83(m, 3H), 6.99-7.09(m, 3H),7.36(d, J=2.7 Hz, 1H), 7.55-7.60(m, 1H) IR (KBr): 3431, 2923, 2550,1654, 1604, 1480, 1455, 1376, 1357, 1284, 971 cm⁻¹ Ib-440 mp 193-195°C.; ¹H NMR (CDCl₃) δ 1.74(s, 3H), 1.78(s, 3H), 2.21(s, 3H), 2.28(s, 3H),3.72(d, J=6.9 Hz, 2H), 5.35(t, J=6.9 Hz, 1H), 6.40(dd, J=12.3, 2.1 Hz,1H), 6.46(dd, J=8.4, 2.4 Hz, 1H), 6.67(dd, J=9.3, 0.6 Hz, 1H), 7.04(t,J=8.4 Hz, 1H), 7.07(s, 1H), 7.11(s, 1H), 7.39(dd, J=2.4, 0.6 Hz, 1H),7.56(dd, J=9.3, 2.4 Hz, 1H); IR (KBr): 3413, 3302, 1660, 1620, 1497,1466, 1421, 1337, 1232, 1174, 835 cm⁻¹

 

TABLE 135 Ib-441 mp 247-249° C.; ¹H NMR (CDCl₃) δ 1.78(s, 3H); 1.82(s,3H); 1.96(s, 6H); 2.04 (s, 6H); 4.64(d, J=6.9 Hz, 2H); 5.58(m, 1H);6.72(d, J=9.3 Hz, 1H); 6.80- 6.92(m, 2H); 7.05(dt, J=1.2, 8.4 Hz, 1H);7.22(d, J=1.8 Hz, 1H); 7.35(ddd, J=1.8, 2.4, 9.3 Hz, 1H); IR (KBr):3444, 2917, 1661, 1619, 1512, 1294, 1262 cm⁻¹. Ib-442 mp 172-176° C.; ¹HNMR (CDCl₃) δ 1.78(s, 3H); 1.82(s, 3H); 1.95(s, 6H); 2.05 (s, 6H);4.64(d, J=6.9 Hz, 2H); 5.57(m, 1H); 6.75-7.25(m, 5H); 10.81(br s, 1H);IR (KBr): 2925, 1689, 1677, 1592, 1514, 1295, 1264, 1243, 1113, 1008cm⁻¹. Ib-443 mp 240-242° C.; ¹H NMR (CDCl₃) δ 1.77(s, 3H); 1.82(s, 3H);1.96(s, 6H); 2.06 (s, 6H); 4.64(d, J=6.3 Hz, 2H); 5.57(m, 1H);6.74-7.09(m, 3H); 7.22(d, J= 1.2 Hz, 1H); 8.42(d, J=1.2 Hz, 1H); IR(KBr): 2916, 1655, 1616, 1512, 1261 cm⁻¹. Ib-539 ¹HMR(CDCl₃): δ 1.59(3H,s), 1.74(3H, s), 1.79(3H, s), 1.83(3H, s), 2.20(3H, s), 2.28(3H, s),4.32(2H, d, J 7.2 Hz), 4.89(2H, d, J 6.9 Hz), 5.32(1H, bt, J 7.2 Hz),5.58(2H, bt, J 6.9 Hz), 5.81(2H, bs), 6.83(1H, d, J 8.4 Hz), 7.14(2H, bs7.03-7.30(3H), 7.60(1H, dd, J 8.4 Hz, 2.4 Hz), 8.18(1H, d, J 2.4 Hz).Ib-540 ¹HNMR (CDCl₃): δ 1.58(3H, s), 1.73(3H, s), 1.80(3H, s), 1.82(3H,s), 2.20 (3H, s), 2.28(3H, s), 2.33(1H, bs), 4.25(2H, bs), 4.30(2H, d, J6.9 Hz), 4.88 (2H, d, J 6.9 Hz), 5.30(1H, bt, J 6.9 Hz), 5.58(2H, bt, J6.9 Hz), 5.90(2H, bs), 6.83(1H, d, J 8.4 Hz), 6.95-7.30(3H), 7.13(2H,bs), 7.60(1H, dd, J 8.4 Hz, 2.4 Hz, 8.18 1H, d, J 2.4 Hz.) Ib-541¹HMR(CDCl₃): δH 1.58(3H, s), 1.73(3H, s), 1.79(3H, s), 1.82(3H, s),2.20(3H, s), 2.28(3H, s), 2.71(4H, s), 4.29(2H, d, J 7.2 Hz), 4.88(2H,d, J 6.9 Hz), 5.30(1H, bt, J 6.9 Hz), 5.57(2H, bt, J 7.2 Hz), 5.80(2H,bs,), 6.82(1H, d, J 8.1 Hz), 6.97-7.27(3H), 7.13(1H, d, J 2.4 Hz),7.60(1H, dd, J 8.1 Hz, 2.4 Hz), 8.18(1H, bs). Ic-1 119-120° C., ¹H-NMR(CDCl₃) δ 1.76(3H, s), 1.82(3H, s), 2.17(3H, s), 2.24(3H, s), 4.61(2H,d, J=6.8), 4.63(1H, s), 5.52(1H, br t, J=6.8), 5.71(1H, s), 6.66 (1H,s), 6.76(JH, dd, J=2.2, 8.3), 6.80(2H, d, J=8.3), 6.86-6.91(4H, m), 7.07(1H, s) Ic-2 oil, ¹H-NMR (CDCl₃) δ 1.75(3H, s), 1.78(3H, s), 2.17(3H,s), 2.25(3H, s), 3.87 (3H, s), 4.62(2H, d, J=6.6), 4.67(1H, s), 5.56(1H,br t, J=6.6), 6.68(1H, s), 6.79-6.93(7H, m), 7.09(1H, s) Ic-3 oil,¹H-NMR (CDCl₃) δ 2.18(3H, s), 2.22(3H, s), 3.14(3H, s), 5.16(2H, s),5.71 (1H, s), 6.77(1H, dd, J=2.0, 8.3), 6.81(1H, s), 6.93-6.99(4H, m),7.10(1H, s), 7.22(2H, d, J=9.0), 7.39-7.47(5H, m) Ic-4 oil, ¹H-NMR(CDCl₃) δ 2.19(3H, s), 2.21(3H, s), 3.11(3H, s), 3.15(3H, s), 5.15 (2H,s), 6.82(1H, s), 6.95(2H, d, J=9.3), 7.10(1H, s), 7.11(1H, d, J=8.3),7.21(1H, dd, J=2.2, 8.3), 7.23(2H, d, J=9.3), 7.31(1H, d, J=2.2), 7.37-7.49(5H, m) Ic-5 oil, ¹H-NMR (CDCl₃) δ 2.19(3H, s), 2.20(3H, s),3.14(3H, s), 3.91(3H, s), 5.20 (2H, s), 6.79(1H, dd, J=2.0, 8.1),6.81(1H, s), 6.86(1H, d, J=2.0), 6.93(1H, d, J=8.1), 6.95(2H, d, J=9.0),7.11(1H, s), 7.22(2H, d, J=9.0), 7.32-7.49 (5H, m) Ic-6 oil, ¹H-NMR(CDCl₃) δ 1.77(3H, s), 1.82(3H, s), 2.19(3H, s), 2.21(3H, s), 3.14 (3H,s), 3.22(3H, s), 4.63(2H, d, J=6.8), 5.51(1H, br t, J=6.8), 6.82(1H, s),6.95(2H, d, J=9.0), 7.04(1H, d, J=8.3), 7.11(1H, s), 7.21(1H, dd, J=2.2,8.3), 7.23(2H, d, J=9.0), 7.29 1H, d, J=2.2)

 

TABLE 136 Ic-7  oil, ¹H-NMR (CDCl₃) δ 1.76(3H, s), 1.80(3H, s), 2.20(3H,s), 2.22(3H, s), 3.15(3H, s), 3.89(3H, s), 4.63(2H, d, J=6.8), 5.57(1H,br t, J=6.8), 6.81- 6.85(3H, m), 6.93(1H, d, J=8.8), 6.96(2H, d, J=8.8),7.13(1H, s), 7.22(2H, d, J=8.8) Ic-8  162-163° C., ¹H-NMR (CDCl₃) δ2.14(3H, s), 2.26(3H, s), 3.55(2H, br s), 3.89 (3H, s), 5.19(2H, s),6.64(1H, s), 6.68(2H, d, J=8.8), 6.77(1H, dd, J=2.0, 8.7), 6.84(2H, d,J=8.8), 6.85(1H, d, J=2.0), 6.91(1H, d, J=8.7), 7.06(1H, s),7.31-7.49(5H, m) Ic-9  111-112° C., ¹H-NMR (CDCl₃) δ 1.75(3H, s),1.79(3H, s), 2.16(3H, s), 2.27 (3H, s), 3.56(2H, br s), 3.87(3H, s),4.62(2H, d, J=6.8), 5.56(1H, br t, J=6.8), 6.65(1H, s), 6.68(2H, d,J=9.0), 6.79-6.92(5H, m), 7.08(1H, s) Ic-12 oil, ¹H-NMR (CDCl₃) δ2.14(3H, s), 2.28(3H, s), 2.93(6H, s), 3.89(3H, s), 5.19(2H, s),6.64(1H, s), 6.74(2H, d, J=9.0), 6.78(1H, dd, J=2.0, 8.3), 6.85 (1H, d,J=2.0), 6.91(1H, d, J=8.3), 6.93(2H, d, J=9.0), 7.31-7.49(5H, m) Ic-14oil, ¹H-NMR (CDCJ3) δ 1.75(3H, s), 1.79(3H, s), 2.16(3H, s), 2.28(3H,s), 2.93(6H, s), 3.87(3H, s), 4.62(2H, d, J=6.8), 5.56(1H, br t, J=6.8),6.65 (1H, s), 6.75(2H, d, J=9.0), 6.80-6.83(2H, m), 6.90(1H, d, J=8.6),6.93(2H, d, J=9.0), 7.08(1H, s) Ic-16 119-120° C., ¹H-NMR (CDCl₃) δ2.13(3H, s), 2.27(3H, s), 3.01(6H, s), 6.78 (1H, d, J=9.3), 6.80(2H, d,J=8.8), 6.89(1H, s), 7.16(1H, s), 7.22(2H, d, J= 8.8), 8.04(1H, dd,J=2.7, 9.3), 8.39(1H, d, J=2.7) Ic-17 80-82° C., ¹H-NMR (CDCl₃) δ2.17(3H, s), 2.30(3H, s), 2.98(6H, s), 3.61(2H, br s), 6.50(1H, s),6.55(1H, dd, J=2.7, 8.6), 6.77(2H, d, J=9.0), 6.81(1H, d, J=2.7),6.82(1H, d, J=8.6), 7.07(1H, s), 7.20(2H, d, J=9.0), Ic-18 141-142° C.,¹H-NMR (CDCl₃) δ 2.21(3H, s), 2.22(3H, s), 3.00(6H, s), 3.03 (3H, s),6.41(1H, br s), 6.71(1H, s), 6.78(2H, d, J=8.8), 6.82(1H, d, J=8.8),7.06(1H, dd, J=2.7, 8.8), 7.11(1H, s), 7.21(2H, d, J=8.8), 7.39(1H, d,J= 2.7) Ic-19 138-139° C., ¹H-NMR (CDCl₃) δ 2.20(3H, s), 2.22(3H, s),3.00(6H, s), 6.72 (1H, s), 6.78(2H, d, J=8.8), 6.85(1H, d, J=8.8),7.12(1H, s), 7.21(2H, d, J=8.8), 7.35(1H, dd, J=2.7, 8.8), 7.77(1H, d,J=2.7), 7.82(1H, br s), Ic-20 oil, ¹H-NMR (CDCl₃) δ 1.73(3H, s),1.77(3H, s), 2.16(3H, s), 2.31(3H, s), 2.98(6H, s), 3.67(2H, d, J=6.6),5.33(1H, br t, J=6.6), 6.48(1H, dd, J=2.7, 8.8), 6.49(1H, s), 6.71(1H,d, J=2.7), 6.77(2H, d, J=8.8), 6.85(1H, d, J= 8.8), 7.07(1H,s), 7.20(2H,d, J=8.8) Ic-23 126-128° C., ¹H-NMR (CDCl₃) δ 1.76(3H, s), 1.82(3H, s),2.26(3H, s), 2.35 (3H, s), 4.58(1H, br s), 4.61(2H, d, J=6.8), 4.96(2H,s), 5.52(1H, br t, J= 6.8), 5.72(1H, s), 6.75-6.81(3H, m), 6.89-6.92(4H,m), 7.08(1H, s), 7.27(1H, s) Ic-24 oil, ¹H-NMR (CDCl₃) δ 1.76(3H, s),1.81(3H, s), 2.26(3H, s), 2.35(3H, s), 3.21(3H, s), 4.53(1H, s),4.62(2H, d, J=6.8), 4.96(2H, s) 5.50(1H, br t, J= 6.8), 6.78(2H, d,J=9.0), 6.90(2H, d, J=9.0), 7.03(1H, d, J=8.5), 7.07 (1H, s), 7.20(1H,dd, J=2.2, 8.5), 7.28(1H, s), 7.29(1H, d, J=2.2) Ic-25 146-147° C.,¹H-NMR (CDCl₃) δ 1.75(3H, s), 1.79(3H, s), 2.25(3H, s), 2.26 (3H, s),3.86(3H, s), 4.62(2H, d, J=6.8), 4.78(1H, s), 5.02(2H, s), 5.56(1H, brt, J=6.8), 6.79-6.82(3H, m), 6.86(2H, d, J=8.5), 6.90(1H, d, J=8.8),7.04(1H.s), 7.35(2H, d, J=8.5) Ic-32 123-124° C., ¹H-NMR (CDCl₃) δ1.76(3H, s), 1.81(3H, s), 2.26(6H, s9, 3.17 (3H, s), 3.21(3H, s),4.61(2H, d, J=6.8), 5.10(2H, s), 5.50(1H, br t, J=6.8), 6.76(1H, s),7.02(1H, d, J=8.3), 7.04(1H, s), 7.18(1H, dd, J=2.2, 8.3), 7.27 (1h, d,J=2.2), 7.33(2H, d, J=8.8), 7.53(2H, d, J=8.8)

 

TABLE 137 Ic-33 125-127° C., ¹H-NMR (CDCl₃) δ 1.75(3H, s), 1.79(3H, s),2.24(3H, s), 2.35 (3H, s), 3.87(3H, s), 4.21(2H, s9, 4.61(2H, d, J=6.6),5.56(1H, br t, J= 6.59(2H, d, J=8.8), 6.73(2H, d, J=8.8), 6.81-6.85(2H,m), 6.92(1H, d, J= 8.8), 7.08(1H, s), (7.23 1H, s) Ic-35 141-142° C.,¹H-NMR (CDCl₃) δ 1.77(3H, s), 1.82(3H, s), 2.30(3H, s), 2.40 (3H, s),4.61(2H, d, J=6.8), 4.79(1H, s), 5.53(1H, br t, J=6.8), 5.70(1H, s),6.79(1H, dd, J=2.2, 8.3), 6.84(2H, d, J=8.8), 6.91(1H, d, J=8.3), 6.93(1H, d, J=2.2), 6.97(1H, d, J=16.1) 7.04(1H, s), 7.18(1H, d, J=16.1),7.43 (2H, d, J=8.8), 7.46 1H, s). Ic-38 140-142° C., ¹H-NMR (CDCl₃) δ1.77(3H, s), 1.82(3H, s), 2.30(3H, s), 2.41 (3H, s), 3.16(3H, s),3.22(3H, s), 4.63(2H, d, J=6.8), 5.51(1H, br t, J=6.8), 7.02(1H, d,J=15.4), 7.04(1H, d, J=8.3), 7.05(1H, s), 7.22(1H, dd, J=2.2, 8.3),7.29(2H, d, J=8.8), 7.30(1H, d, J=2.2), 7.31(1H, d, J=15.4), 7.48(1H, s,7.57(2H, d, J=8.8) Ic-43 146-147° C., ¹H-NMR (CDCl₃) δ 1.75(3H, s),1.79(3H, s), 2.25(3H, s), 2.48 (3H, s), 3.88(3H, s), 4.62(2H, d, J=6.8),5.04(1H, s), 5.56(1H, br t, J=6.8), 6.81-6.85(4H, m), 6.92(1H, d,J=8.8), 7.10(1H, s), 7.38(1H, s), 7.44(2H, d, J=8.6) Ic-44 121-122° C.,¹H-NMR (CDCl₃) δ 1.76(3H, s), 1.79(3H, s), 2.26(3H, s), 2.49 (3H, s),3.17(3H, s), 3.88(3H, s), 4.63(2H, d, J=6.8), 5.56(1H, br t, J=6.8),6.81-6.85(2H, m), 6.93(1H, d, J=8.8), 7.12(1H, s), 7.29(2H, d, J=8.8),7.40 1H, s), 7.59(2H, d, J=8.8) Ic-47 oil, ¹H-NMR (CDCl₃) δ 1.76(3H, s),1.79(3H, s9, 2.26(3H, s), 2.29(3H, s), 3.89(3H, s), 4.64(2H, d, J=6.6),5.57(1H, br t, J=6.6), 5.82(1H, s), 6.85- 6.88(2H, m), 6.90(2H, d,J=8.8), 6.95(1H, d, J=8.5), 7.14(1H, s), 7.18(1H, s), 7.81(2H, d, J=8.8)Ic-49 oil, ¹H-NMR (CDCl₃) δ 1.75(3H, s), 1.79(3H, s), 2.07(1H, d, 3.7),2.21(3H, s), 2.28(3H, s), 3.87(3H, s), 4.62(2H, d, J=6.8), 4.81(1H, s),5.56(1H, br t, J= 6.8), 5.96(1H, d, J=3.7), 6.81(2H, d,J=8.8)6.82-6.85(2H, m), 6.92(1H, d, J=8.8), 7.02(1H, s), 7.25(2H, d,J=8.8), 7.42(1H, s) Ie-4  170-170.5° C., ¹H-NMR (CDCl₃) δ 5.15(2H, s),5.75(1H, s), 6.94(1H, dd, J= 0.7, 8.5), 6.98(2H, m), 7.06-7.16(5H, m),7.37-7,44(5H, m), 7.83(1H, dd, J= 2.4, 8.5), 8.34(1H, dd, J=0.7, 2.4)Ie-5  122-122.5° C. Ie-6  175-176° C., ¹H-NMR (CDCl₃) δ 2.38(3H, s),5.11(2H, s), 5.75(1H, s), 6.94 (1H, d, J=8.3), 6.98(2H, m),7.05-7.17(5H, m), 7.22(2H, d, J=8.1), 7.32 2H, d, J=8.1), 7.83(1H, dd,J=2.4, 8.6), 8.34(1H, d, J=2.4) Ie-7  144.5-145,5° C., ¹H-NMR (CDCl₃) δ2.37(3H, s), 3.11(3H, s), 5.12(2H, s), 6.96 (1H, d, J=8.6),7.10-7.15(5H, m), 7.21(2H, d, J=8.1), 7.33(2H, d, J=8.1), 7.39(1H, dd,J=2.2, 8.6), 7.47(1H, d, J=2.2), 7.83(1H, dd, J=2.7, 8.6), 8.33 (1H, d,J=2.7) Ie-8  125-127° C., ¹H-NMR (CDCl₃) δ 1.76(3H, s), 1.81(3H, s),4.61(2H, d, J=6.8), 5.51(1H, br t, J=6.8), 5.76(1H, s), 6.91-7.01(3H,m), 7.06-7.16(5H, m), 7.83 (1H, dd, J=2.4, 8.6), 8.34(1H, dd, J=0.7,2.4) Ie-9  127-128° C., ¹H-NMR (CDCl₃) δ 1.76(3H, s), 1.81(3H, s),3.22(3H, s), 4.62 (2H, d, J=6.8), 5.48(1H, br t, J=6.8), 6.96(1H, dd,J=0.7, 8.6), 7.06-7.15 (5H, m), 7.40(1H, dd, J=2.2, 8.6), 7.46(1H, d,J=2.2), 7.83(1H, dd, J=2.4, 8.6), 8.33(1H, dd, J=0.7, 2.4) Ie-13153-154° C., ¹H-NMR (CDCl₃) δ 2.25(3H, s), 3.10(3H, s), 3.78(3H, s),5.16 (2H, s), 7.13(2H, s), 7.19-7.25(4H, m), 7.36-7.48(7H, m)

 

TABLE 138 Ie-14 oil, ¹H-NMR (CDCl₃) δ 2.23(3H, s), 2.39(3H, s), 3.77(3H,s), 5.09(2H, s), 5.74(1H, s), 6.69(1H, dd, J=1.8, 8.5), 6.82(1H, d,J=1.8), 6.98(1H, d, J=8.5), 7.18- 7.43(9H, m) Ie-15 166-167° C., ¹H-NMR(CDCl₃) δ 2.25(3H, s), 2.38(3H, s), 3.09(3H, s), 3.78 (3H, s), 5.11(2H,s), 7.12(2H, s), 7.15-7.44(10H, m) Ie-17 132-133° C., ¹H-NMR (CDCl₃) δ2.25(3H, s), 3.10(3H, s), 3.79(3H, s), 3.83 (3H, s), 5.16(2H, s),6.91(2H, d, J=9.1), 6.94-7.23(5H, m), 7.36-7.48(5H, m) Ie-18 oil, ¹H-NMR(CDCl₃) δ 2.24(3H, s), 2.39(3H, s), 3.78(3H, s), 3.83(3H, s), 5.09(2H,s), 5.71(1H, d, J=1.8), 6.68(1H, dd, J=1.8, 7.9), 6.82(1H, d, J= 1.8),6.90(2H, d, J=1.8), 6.98(1H, d, J=7.9), 7.16(2H, d, J=1.8), 7.23(2H, d,J=7.9), 7.33(2H, d, J=7.9) Ie-19 113-114° C., ¹H-NMR (CDCl₃) δ 2.24(3H,s), 2.38(3H, s), 3.09(3H, s), 3.78 (3H, s), 3.83(3H, s), 5.11(2H, s),6.91(2H, d, J=8.5), 7.34(2H, d, J=8.5) Ie-23 157-158° C. Ie-24 114-116°C., ¹H-NMR (CDCl₃) δ 1.76(3H,s), 1.82(3H, s), 2.23(3H, s), 3.78 (3H, s),4.60(2H, d, J=6.8), 5.52(1H, br t, J=6.8), 5.74(1H, s), 6.67(1H, dd,J=2.0, 8.3), 6.79(1H, d, J=2.0), 6.91(1H, d, J=8.3), 7.07(1H, dd, J=8.3,9.3), 7.21(1H, dd, J=4.6, 8.3) Ie-25 107-108° C., ¹H-NMR (CDCl₃) δ1.76(3H,s), 1.81(3H, s), 2.25(3H, s), 3.21 (3H, s), 3.79(3H, s),4.62(2H, d, J=6.6), 5.50(1H, br t, J=6.6), 7.03-7.23 (7H, m) Ie-27177-178° C., ¹H-NMR (CDCl₃) δ 2.24(3H, s), 3.10(3H, s), 3.92(3H, s),5.16 (2H, s), 6.99-7.49(11H, m), 7.66(2H, d, J=7.9) Ie-28 170-172° C.,¹H-NMR (CDCl₃) δ 2.22(3H, s), 2.39(3H, s), 3.92(3H, s), 5.09 (2H, s),5.71(1H, s), 6.71(1H, dd, J=1.8, 7.9), 6.84(1H, d, J=1.8), 6.98(1H, d,J=7.9), 7.03(2H, d, J=7.3), 7.23(2H, d, J=7.9), 7.29-7.36(3H, m), 7.67(2H, dd, J=1.2, 8.5) Ie-29 169-170° C., ¹H-NMR (CDCl₃) δ 2.24(3H, s),2.38(3H, s), 3.10(3H, s), 3.92 (3H, s), 5.11(2H, s), 6.99-7.37(10H, m),7.66(2H, d, J=7.9) Ie-31 150-15I° C., ¹H-NMR (CDCl₃) δ 2.22(3H, s),3.10(3H, s), 3.81(3H, s), 3.88 (3H, s), 5.15(2H, s), 6.87(1H, s),6.89(2H, d, J=9.1), 7.09(1H, d, J=8.5), 7.14(1H, dd, J=1.8, 8.5),7.24(1H, d, J=1.8), 7.36-7.53(5H, m), 7.55(2H, d, J=9.1) Ie-32 175-176°C., ¹H-NMR (CDCl₃) δ 2.20(3H, s), 2.39(3H, s), 3.81(3H, s), 3.88 (3H,s), 5.09(2H, s), 5.68(1H, s), 6.70(1H, dd, J=1.8, 7.9), 6.83(1H, d, J=1.8), 6.85(1H, br s), 6.88(2H, d, J=9.2), 6.97(1H, d, J=7.9), 7.23(2H,d, J= 7.9), 7.34(2H, d, J=7.9), 7.55(2H, d, J=9.2) Ie-33 176-177° C.,¹H-NMR (CDCl₃) δ 2.22(3H, s), 2.37(3H, s), 3.09(3H, s), 3.81 (3H, s),3.88(3H, s), 5.10(2H, s), 6.87(1H, s), 6.89(2H, d, J=8.5), 7.09(1H, d,J=8.5), 7.14(1H, dd, J=1.8, 8.5), 7.22(2H, d, J=8.5), 7.23(1H, s), 7.34(2H, d, J=8.5), 7.55(2H, d, J=8.5) Ie-38 188-189° C., ¹H-NMR (CDCl₃) δ2.21(3H, s), 2.39(3H, s), 3.89(3H, s), 5.09 (2H, s), 5.68(1H, s),6.70(1H, dd, J=1.8, 7.9), 6.83(1H, d, J=1.8), 6.91-7.06 (4H, m),7.23(2H, d, J=8.5), 7.34(2H, d, J=8.5), 7.56-7.65(2H, m) Ie-39 194-195°C., ¹H-NMR (CDCl₃) δ 2.23(3H, s), 2.38(3H, s), 3.09(3H, s), 3.89 (3H,s), 5.11(2H, s), 6.94-7.21(5H, m), 7.22(2H, d, J=1.8), 7.23(1H, s), 7.35(2H, d, J=7.9), 7.57-7.63(2H, m) Ie-40 159-160° C., ¹H-NMR (CDCl₃) δ1.76(3H, s), 1.82(3H, s), 2.21(3H, s), 3.89 (3H, s), 4.60(2H, d, J=6.7),5.52(1H, t, J=6.7), 5.71(1H, s), 6.68(1H, dd, J=1.8, 8.5), 6.81(1H, d,J=1.8), 6.90(1H, d, J=8.5), 7.02(2H, t, J=8.5), 7.57-7.65 2H, m)

 

TABLE 139 Ie-41 142-143° C., ¹H-NMR (CDCl₃) δ 1.76(3H, s), 1.81(3H, s),2.24(3H, s), 3.21 (3H, s), 3.89(3H, s), 4.62(2H, d, J=7.3), 5.50(1H, t,J=7.3), 6.94(1H, s), 6.99-7.08(3H, m), 7.13(1H, dd, J=2.4, 8.5),7.22(1H, d, J=2.4), 7.56-7.65 (2H, m) If-10 151-152° C., ¹H-NMR (CDCl₃)δ 2.18(3H, s), 3.09(3H, s), 3.75-3.81(8H, m), 3.83(3H, s), 5.14(2H, s),7.08(1H, d, J=8.5), 7.11(1H, dd, J=1.7, 8.5), 7.21 (1H, d, J=1.7),7.35-7.47(5H, m) If-14 140-141° C., ¹H-NMR (CDCl₃) δ 2.18(3H, s),2.36(3H, s), 2.48(4H, t, J=5.5), 3.09(3H, s), 3.83(3H, s), 3.87(4H, t,J=5.5), 5.14(2H, s), 7.07(1H, d, J=8.5), 7.11(1H, dd, J=1.8, 8.5),7.21(1H, d, J=1.8), 7.33-7.49(5H, m) If-18 152-153° C., ¹H-NMR (CDCl₃) δ2.20(3H, s), 3.09(3H, s), 3.26(4H, t, J=5.5), 3.86(3H, s), 4.01(4H, t,J=5.5), 5.14(2H, s), 6.90(1H, d, J=7.3), 7.00(2H, d, J=7.3), 7.08(1H, d,J=8.5), 7.12(1H, dd, J=1.8, 8.5), 7.21-7.49(8H, m) If-26 195-197° C.,¹H-NMR (CDCl₃) δ 2.44(3H, s), 3.12(3H, s), 4.05(3H, s), 5.18 (2H, s),7.14-7.21(2H, m), 7.28(1H, m), 7.38-7.48(5H, m), 8.17(1H, s), 9.22 (1H,s) If-29 mp 122.5-123.5° C., ¹H NMR (CDCl₃) δ 1.74(s, 3H), 1.78(s, 6H),1.81 (s, 3H), 2.36(s, 3H), 2.57 (br s, 3H), 3.74(d, J=6.9 Hz, 2H),4.88(d, J=6.9 Hz, 2H), 5.37(br t, J=6.9 Hz, 1H), 5.56(br t, J=6.9 Hz,1H), 6.68(d, J=8.7 Hz, 2H), 6.84(dd, J=0.6, 8.7, 1H), 7.19(d, J=8.7 Hz,2H), 7.43(br s, 1H), 7.83(dd, J=2.4, 8.7 Hz, 1H), 8.38(dd, J=0.6, 2.4Hz, 1H) If-30 mp 122.5-123.5° C., ¹H NMR (CDCl₃) δ 1.78(s, 3H), 1.81(s,3H), 2.37(s, 3H), 2.58(br s, 3H), 4.88(d, J=7.2 Hz, 2H), 5.56(br t,J=7.2 Hz, 1H), 6.77(d, J=8.4 Hz, 2H), 6.85(dd, J=0.6, 8.4, 1H), 7.16(d,J=8.4 Hz, 2H), 7.45(br s, 1H), 7.84(dd, J=2.4, 8.4 Hz, 1H), 8.38(dd,J=0.6, 2.4 Hz, 1H) Ig-1 mp 176-177° C.; ¹H NMR (CDCl₃) δ 1.80(s, 3H);1.83(s, 3H); 1.98(s, 6H); 2.00 (s, 6H); 4.51(br s, 2H); 4.88(d, J=6.9Hz, 2H); 5.90(m, 1H); 6.63(m, 1H); 6.85(ddd, J=0.9, 1.5, 8.4 Hz, 1H);7.29(ddd, J=2.1, 4.2, 8.4 Hz, 1H); 7.39 (ddd, J=1.2, 2.4, 8.4 Hz, 1H);7.90(m, 1H); 7.97 (m, 1H); IR (KBr): 3464, 3302, 3164, 2916, 1638, 1603,1512, 1491, 1459, 1385, 1360, 1300, 1279, 1242 cm − 1. Ig-2 mp 162-164°C.; ¹H NMR (CDCl₃) δ 1.75(s, 3H); 1.78(s, 3H); 1.80(s, 3H); 1.83 (s,3H); 1.98(s, 6H); 2.02(s, 6H); 3.91(t, J=5.7 Hz, 2H); 4.51(br t, 1H);4.88 (d, J=7.2 Hz, 2H); 5.38(m, 1H); 5.59(m, 1H); 6.50(m, 1H); 6.85(ddd,J= 0.9, 1.5, 8.7 Hz, 1H); 7.27(ddd, J=2.1, 4.2, 8.7 Hz, 1H); 7.40(ddd,J=2.4, 3.3, 8.4 Hz, 1H); 7.92(m, 1H); 7.98(dt, J=0.9, 2.4 Hz, 1H); IR(KBr): 3420, 3242, 2913, 1605, 1503, 1462, 1378, 1350, 1277, 1240 cm⁻¹.Ig-3 ¹H NMR (300 MHz, CDCl₃) δ 1.80(s, 3H), 1.83(s, 3H), 2.07(s, 3H),2.09(s, 3H), 3.34(s, 3H), 3.36(s, 3H), 4.59(br s, 2H), 4.89(d, J=7.2 Hz,2H), 5.54- 5.62(m, 1H), 6.62(d, J=8.4 Hz, 1H), 6.84(dd, J=8.4, 0.7 Hz,1H), 7.45(dd, J=8.4, 2.2 Hz, 1H), 7.54(dd, J=8.4 Hz, 1H), 8.04(d, J=2.2Hz, 1H), 8.10 (dd, J=2.5, 0.7 Hz, 1H) Ig-4 ¹H NMR (300 MHz, CDCl₃) δ1.76(s, 3H), 1.78(d, J=0.9 Hz, 3H), 1.80(d, J=0.9 Hz, 3H), 1.83(d, J=0.9Hz, 3H), 2.07(s, 3H), 2.10(s, 3H), 3.34(s, 3H), 3.36(s, 3H), 3.91(t,J=6.0 Hz, 2H), 4.58(br s, 1H), 4.88(d, J=6.9 Hz, 2H), 5.34-5.41(m, 1H),5.55-5.62(m, 1H), 6.49(dd, J=8.6, 0.7 Hz, 1H), 6.84(dd, J=8.3, 0.8 Hz,1H), 7.43(dd, J=8.6, 2.3 Hz, 1H), 7.55(dd, J=8.3, 2.3 Hz, 1H), 8.05(dd,J=2.3, 0.7 Hz, 1H), 8.11(dd, J=2.3, 0.8 Hz, 1H)

 

TABLE 140 Ig-5 mp 126-128 2 C.; ¹H NMR (CDCl₃) δ 1.75(s, 6H), 1.78(s,6H), 2.07(s, 6H), 2.55(s, 6H), 3.90(t, J=6.0 Hz, 4H), 4.53(m, 2H),5.37(t, J=6.6 Hz, 2H), 6.47(dd, J=8.4, 0.9 Hz, 2H), 7.17(dd, J=8.4, 2.4Hz, 2H), 7.82(dd, J=2.4, 0.9 Hz, 2H); IR (KBr): 3222, 1607, 1532, 1389,1313, 981, 811 cm⁻¹ Ig-6 ¹H NMR (300 MHz, CDCl₃) δ 1.75(s, 6H), 1.78(d,J=0.9 Hz, 6H), 2.10(s, 6H), 3.36(s, 6H), 3.91(t, J=0.9 Hz, 4H), 4.53(t,J=5.0 Hz, 2H), 5.34-5.42 (m, 2H), 6.48(d, J=8.5 Hz, 2H), 7.42(dd, J=8.5,2.3 Hz, 2H), 8.05(dd, J= 2.3, 0.8 Hz, 2H) Ig-7 ¹H NMR (300 MHz, CDCl₃) δ1.80(s, 3H), 1.83(s, 3H), 2.08(s, 3H), 2.12(s, 3H), 3.34(s, 3H), 3.39(s,3H), 4.89(d, J=6.9 Hz, 2H), 5.17(br s, 2H), 5.54-5.62(m, 1H), 6.84(dd,J=8.6, 0.8 Hz, 1H), 7.53(dd, J=8.6, 2.3 Hz, 1H), 8.09(dd, J=2.3, 0.8 Hz,1H), 8.32(s, 2H) Ig-8 ¹H NMR (300 MHz, CDCl₃) δ 1.76(s, 3H), 1.78(s,3H), 1.80(s, 3H), 1.83(s, 3H), 2.08(s, 3H), 2.13(s, 3H), 3.34(s, 3H),3.40(s, 3H), 4.05(s, J=6.2 Hz, 2H), 4.88(d, J=6.9 Hz, 2H), 5.14-5.18(m,1H), 5.35-5.42(m, 1H), 5.55-5.61 (m, 1H), 6.85(dd, J=8.5, 0.7 Hz, 1H),7.54(dd, J=8.5, 2.7 Hz, 1H), 8.10 (dd, J=2.7, 0.7 Hz, 1H), 8.30(s, 2H)Ig-9 ¹H NMR (300 MHz, CDCl₃) δ 1.79(s, 3H), 1.83(d, J=0.9 Hz, 3H),2.07(s, 3H), 2.08(s, 3H), 3.34(s, 3H), 3.40(s, 3H), 4.67(br s, 2H),4.89(d, J=7.2 Hz, 2H), 5.54-5.62(m, 1H), 6.84(dd, J=8.6, 0.7 Hz, 1H),7.53(dd, J=8.6, 2.5 Hz, 1H), 8.09(dd, J=2.5, 0.7 Hz, 1H), 8.12(d, J=1.5Hz, 1H), 8.15(d, J= 1.5 Hz, 1H)  Ig-10 ¹H NMR (300 MHz, CDCl₃) δ 1.77(s,3H), 1.79(s, 6H), 1.83(s, 3H), 2.07(s, 3H), 2.09(s, 3H), 3.34(s, 3H),3.41(s, 3H), 3.99(t, J=5.7 Hz, 2H), 4.62(br s, 1H), 4.88(d, J=6.9 Hz,2H), 5.34-5.42(m, 1H), 5.55-5.62(m, 1H), 6.84(dd, J=8.4, 0.8 Hz, 1H),7.53(dd, J=8.4, 2.5 Hz, 1H), 8.02(d, J=1.5 Hz, 1H), 8.09(dd, J=2.5, 0.8Hz, 1H)

 

Experiment 1 Suppressive Effect on a Mitogenic Activity of MouseSplenocytes in Vitro

In 96-well microtiter plate, 5×10⁵ C3H/HeN mouse splenocytes suspendedin 0.1 ml of 10% fetal bovine serum-fortified RPMI 1640 mediumcontaining 2 mM of sodium bicarbonate, 50 units/ml of penicillin, 50μg/ml of streptomycin and 5×10⁻⁵ M of 2-mercaptoethanol were added.Then, 5 μg/ml of Concanavalin A (Con A) or 10 μg/ml oflipopolysaccharide (LPS) as a mitogen and the compound of apre-determined concentration of the present invention were added to eachwell so that the final volume of each well reached 0.2 ml. Each compoundof the present invention was dissolved in dimethylsulfoxide (DMSO) anddiluted with the above RPMI 1640 medium to adjust the finalconcentration of 100 ng/ml or less. The splenocytes in the 96-wellmicrotiter plate were cultivated at 37° C. for 3 days in an incubatorkeeping the humidity 100%, carbon dioxide 6% and air 95%. Then, 25 μl of6 mg/ml MTT {3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide} (Sigma) was added to the each well and cultivated at 37° C. for4 hours under the same conditions. After the cultivation, 50 μl of 20%sodium dodecyl sulfate (SDS) containing 0.02 N hydrochloric acid wasadded to the generated formazan and the mixture was allowed to stand at37° C. for 24 hours for dissolving formazan. The absorption intensity(OD) of formazan generated in proportion to the number of living cellswas measured with an immunoreader (InterMed) equipped with a 570 nmfilter The Journal of Immunological Method, 65, 55-63, 1983). The 50%inhibitory concentration of a cell proliferation (IC₅₀) was calculatedfrom a correlation between the concentration of the compound of thepresent invention and the absorption intensity.

Experiment 2 Anti-proliferative Activity on EL4 Cells

In 96-well microtiter plate 4×10⁴/0.1 ml of mouse thymoma strain EL4cells were added and 0.1 ml of the compound of the present invention wasadded thereto so that the concentration was in a range of 0-5,000 ng/ml.After the cultivation for 3 days, the IC₅₀ was calculated by the MTTmethod as described in Experiment 1.

The results of Experiments 1 and 2 are shown in Table 141.

TABLE 141 ConA LPS EL-4 Compound IC₅₀ IC₅₀ IC₅₀ No. (ng/ml) (ng/ml)(ng/ml) Ia-2  ≦10 ≦10  33 Ia-42 16 31 200 Ia-43 74 154 500 Ia-45 66 373811 Ia-66 52 39  80 Ia-94 12 21  50 Ib-3  41 145 307 Ib-13 58 179 426Ib-16 3.1 6.7 400 Ib-17 29 60  78 Ib-20 51 196 576 Ib-23 78 283 651Ib-37 92 361 114 Ib-40 16 55  60 Ib-44 60 317 426 Ib-54 <20 53  91 Ib-6592 134 553 Ib-71 18 54  69 Ib-82 <20 <20 <20  Ib-101 42 261 493 Ic-1  48158 473 Ic-14 15 53 207

 

As shown in the above, the compound of the present invention hasimmunosuppressive and anti-allergic effects.

Experiment 3 Suppressive effect on the IgE Production Against ovalbumin(OVA)

1) Animals

BALB/c mice (female, 8-10 weeks old) and Wistar rats (female, 8-10 weeksold) which were bought from Japan SLC, Inc. (Shizuoka) were used.

2) Immunizing Method

BALB/c mice were immunized by an intraperitoneal administration of 0.2ml suspension of 2 μg of ovalbumin (OVA) and 2 mg of aluminium hydroxidegel in physiological saline. After 10 days, blood was collected fromhearts, then sera were separated and stocked at −40° C. till themeasurement of IgE antibody titer.

3) Compounds

After the compound of the present invention was dissolved or suspendedin N,N-dimethylacetoamide, the mixture was diluted 20 times with miglyol812 neutral oil. The obtained solution was orally administered to miceat 0.1 ml per mouse (dose 40 mg/kg). The administration was continuedfor 10 days from the immunizing day to the day before the bloodcollection.

4) Measurement of Anti-OVA IgE Antibody Titer (PCA Titer)

The obtained mouse serum was 2-fold diluted with physiological saline,then each 50 μl of the solution was intradermally injected at dorsalskin of Wistar rats which previously hair cut. After 24 hours, a passivecutaneous anaphylaxis reaction (PCA) was induced by an intravenousinjection of 0.5 ml of physiological saline containing 1 mg of OVA and 5mg of Evans' blue dye. The rats were sacrified 30 minutes later and thehighest dilution giving bluing with a diameter of 5 mm or more wasrecorded as the PCA titer. For example, when a serum is positive for thePCA reaction till 2⁷ times dilution, the anti-OVA IgE antibody titer ofthe mouse is defined as 7. The results are shown in Table 142.

TABLE 142 Compound PCA Titer Ia-356 5.3 Ib-37  0 Ib-69  1.5 Ib-90  1.7Ib-218 5.5 Ib-219 <0 Ib-220 <0 Ib-221 0.3 Ib-222 <0 Ib-223 3.8 Ib-224 0Ib-225 0 Ib-226 0 Ib-227 4.5 Ib-228 2.5 Ib-229 3 Ib-230 0 Ib-231 <0Ib-232 1 Ib-233 2 Ib-234 <0 Ib-235 <0 Ib-239 0 Ib-240 0 Ib-241 0 Ib-2421 Ib-243 2.3 Ib-244 0 Ib-245 5.3 Ib-246 0 Ib-247 0 Ib-248 0 Ib-249 0Ib-250 0 Ib-259 0 Ib-272 5.3 Ib-279 1 Ib-280 0 Ib-281 0 Ib-283 3 Ib-2846.8 Ib-285 2 Ib-293 5 Ib-297 3 Ib-298 2.3 Ib-299 0 Ib-301 3 Ib-302 1.5Ib-305 3 Ib-306 5.3 Ib-307 5 Ib-309 4.3 Ib-310 5.8 Ib-311 6.3 Ib-312 0Ib-322 4 Ib-329 3.8 Ib-330 0.5 Ib-331 <0 Ib-332 2.3 Ib-333 <0 Ib-334 <0Ib-342 <0 Ib-343 0 Ib-344 0 Ib-350 2.3 Ib-351 2.8 Ib-352 <0 Ib-353 2.5Ib-354 <0 Ib-358 <0 Ib-361 <0 Ib-396 <0 Ib-431 6.5 Ib-433 5.5 Ib-439 5.3Ig-2  6.8

 

As shown in the above, the compound of the present invention has asuppressive effect on the IgE production.

Formulation Example 1

The compound of the present invention (Ia-1) 15 mg Starch 15 mg Lactose15 mg Crystalline cellulose 19 mg Polyvinyl alcohol 3 mg Distilled water30 ml Calcium stearate 3 mg

 

After all of the above ingredients except for calcium stearate wereuniformly mixed, the mixture was crushed and granulated, and dried toobtain a suitable size of granules. After calcium stearate was added tothe granules, tablets were formed by compression molding.

Industrial Applicability

As explained in the above experiments, the compound of the presentinvention has a potent immunosuppressive and/or anti-allergic activity.The compound of the present invention is very useful as animmunosuppressant, an anti-allergic agent and/or a suppressant of theIgE production.

What is claimed is:
 1. A compound of the formula (I):

  wherein A ring, B ring and C ring are each independently optionallysubstituted aromatic carbocycle or optionally substituted 5- or6-membered heterocycle which may fuse with benzene ring, W¹, W² and/orW³ represents a single bond when A ring, B ring and/or C ring isoptionally substituted 5-membered heterocycle, X is —O—, —CH₂—, —NR¹—wherein R¹ is hydrogen, optionally substituted lower alkyl, loweralkenyl, lower alkylcarbonyl or optionally substituted loweralkoxycarbonyl or —S(O)p— wherein p is an integer of 0 to 2, Y ishydrogen, optionally substituted lower alkyl, optionally substitutedlower alkenyl, optionally substituted lower alkynyl, optionallysubstituted RC(O) wherein R is hydrogen, alkyl, alkenyl, cycloalkyl oraryl, optionally substituted cycloalkyl, optionally substitutedcycloalkenyl, optionally substituted lower alkoxycarbonyl, optionallysubstituted sulfamoyl, optionally substituted amino, optionallysubstituted aryl or optionally substituted 5- or 6-membered heterocycle,Y may be optionally substituted lower alkoxy when X is —CH₂—, Y may beoptionally substituted lower alkoxycarbonyl, optionally substitutedlower alkylsulfonyl or optionally substituted arylsulfonyl when X is —O—or —NR¹—, one of V¹ and V² is a single bond and the other is a singlebond, an —O— bond, an —NH— bond, an —OCH₂— bond, a —CH₂O— bond, a—CH═CH— bond, a —C≡C— bond, a —CH(OR²)— bond, wherein R² is hydrogen orlower alkyl, a —CO— bond, or an —NHCHR³— bond, wherein R³ is hydrogen orhydroxy, and at least one of A ring, B ring and C ring is optionallysubstituted aromatic carbocycle and at least another one is optionallysubstituted 5- or 6-membered heterocycle which may fuse with benzenering when both of V¹ and V² are single bonds, excluding (i) a compoundwherein B ring is optionally substituted imidazole ring, optionallysubstituted furan ring, optionally substituted thiophene ring,optionally substituted pyrrole ring, optionally substituted oxazolering, or optionally substituted thiazole ring, (ii) a compound whereinboth of A ring and C ring are optionally substituted pyrazole ring and—X—Y is methyl, (iii) a compound wherein one of A ring and C ring isoptionally substituted oxadiazole ring or optionally substitutedtetrazole ring, and provided that (iv) when at least one of A ring, Bring and c ring is optionally pyrimidine ring or when all of A ring, Bring and C ring are optionally substituted benzene ring, (iv-1) C ringis substituted with X′—Y′ at paraposition of V² wherein X′ is the sameas X and Y′ is the same as Y′ and (iv-2) at least one of —X—Y and —X′—Y′is other than unsubstituted lower alkyl, unsubstituted lower alkoxy,unsubstituted alkanoyloxy and unsubstituted lower alkylamino, salt orhydrate thereof.
 2. The compound as claimed in claim 1 wherein A ring isoptionally substituted benzene ring, salt or hydrate thereof.
 3. Thecompound as claimed in claim 1 wherein B ring is optionally substitutedbenzene ring, optionally substituted pyridine ring, optionallysubstituted pyrimidine ring, optionally substituted pyridazine ring,optionally substituted pyrazine ring, or optionally substituted pyrazolering salt or hydrate thereof.
 4. The compound as claimed in claim 1wherein C ring is optionally substituted benzene ring, optionallysubstituted pyridine ring, optionally substituted pyrimidine ring,optionally substituted pyridazine ring, optionally substituted pyrazinering, optionally substituted isoxazole ring, optionally substitutedpyrazole ring, optionally substituted benzothiazole ring, optionallysubstituted morpholine ring, optionally substituted piperazine ring,optionally substituted imidazole ring or optionally substituted triazolering, salt or hydrate thereof.
 5. The compound as claimed in claim 1wherein X is —O— or —NR¹— wherein R¹ is hydrogen, methyl or prenyl, saltor hydrate thereof.
 6. The compound as claimed in claim 1 wherein Y ishydrogen, optionally substituted lower alkyl, optionally substitutedlower alkenyl, lower alkylsulfonyl or optionally substituted acyl, saltor hydrate thereof.
 7. The compound as claimed in claim 1 wherein one ofV¹ and V² is a single bond and the other is a single bond, —O— or —NH—,salt or hydrate thereof.
 8. The compound as claimed in claim 1 wherein Aring is optionally substituted benzene ring, B ring is optionallysubstituted benzene ring, optionally substituted pyridine ring,optionally substituted pyrimidine ring, optionally substitutedpyridazine ring, optionally substituted pyrazine ring, or optionallysubstituted pyrazole ring, C ring is optionally substituted benzenering, optionally substituted pyridine ring, optionally substitutedpyrimidine ring, optionally substituted pyridazine ring, optionallysubstituted pyrazine ring, optionally substituted isoxazole ring,optionally substituted pyrazole ring, optionally substitutedbenzothiazole ring, optionally substituted morpholine ring, optionallysubstituted piperazine ring, optionally substituted imidazole ring oroptionally substituted triazole ring, X is —O— or —NR¹— wherein R¹ ishydrogen, methyl or prenyl, Y is optionally substituted lower alkyl oroptionally substituted lower alkenyl, and one of V¹ and V² is a singlebond and the other is a single bond, —O— or —NH—, salt or hydratethereof.
 9. The compound as claimed in claim 1 wherein two of A ring, Bring and C ring are optionally substituted benzene ring and the other isoptionally substituted 5- or 6-membered heterocycle which may fuse withbenzene ring, salt or hydrate thereof.
 10. A pharmaceutical compositioncomprising the compound of the formula (I):

  wherein A ring, B ring and C ring are each independently optionallysubstituted aromatic carbocycle or optionally substituted 5- or6-membered heterocycle which may fuse with benzene ring, W¹, W² and/orW³ represents a single bond when A ring, B ring and/or C ring isoptionally substituted 5-membered heterocycle, X is —O—, —CH₂—, —NR¹—wherein R¹ is hydrogen, optionally substituted lower alkyl, loweralkenyl, lower alkylcarbonyl or optionally substituted loweralkoxycarbonyl or —S(O)p— wherein p is an integer of 0 to 2, Y ishydrogen, optionally substituted lower alkyl, optionally substitutedlower alkenyl, optionally substituted lower alkynyl, optionallysubstituted RC(O) wherein R is hydrogen, alkyl, alkenyl, cycloalkyl oraryl, optionally substituted cycloalkyl, optionally substitutedcycloalkenyl, optionally substituted lower alkoxycarbonyl, optionallysubstituted sulfamoyl, optionally substituted amino, optionallysubstituted aryl or optionally substituted 5- or 6-membered heterocycle,Y may be optionally substituted lower alkoxy when X is —CH₂—, Y may beoptionally substituted lower alkoxycarbonyl, optionally substitutedlower alkylsulfonyl or optionally substituted arylsulfonyl when X is —O—or —NR¹—, one of V¹ and V² is a single bond and the other is a singlebond, an —O— bond, an —NH— bond, an —OCH₂— bond, a —CH₂O— bond, a—CH═CH— bond, a —C≡C— bond, a —CH(OR²)— bond, wherein R² is hydrogen orlower alkyl, a —CO— bond, or an —NHCHR³— bond, wherein R³ is hydrogen orhydroxy, and at least one of A ring, B ring and C ring is optionallysubstituted aromatic carbocycle and at least another one is optionallysubstituted 5- or 6-membered heterocycle which may fuse with benzenering when both of V¹ and V² are single bonds, excluding (i) a compoundwherein B ring is optionally substituted imidazole ring, optionallysubstituted furan ring, optionally substituted thiophene ring,optionally substituted pyrrole ring, optionally substituted oxazolering, or optionally substituted thiazole ring and (ii) a compoundwherein one of A ring and C ring is optionally substituted oxadiazolering or optionally substituted tetrazole ring, salt or hydrate thereofand a pharmaceutically acceptable carrier.
 11. A method for suppressingan immune response or treating allergic diseases in a patient in needthereof, comprising: administering the pharmaceutical compositionaccording to claim 10 to said patient, wherein said pharmaceuticalcomposition suppresses an immune response or treats allergic diseases insaid patient.
 12. A method for suppressing IgE production in a patientin need thereof, comprising: administering the pharmaceuticalcomposition according to claim 10 to said patient, wherein saidpharmaceutical composition suppresses IgE production in said patient.13. A compound of the formula (Ib′):

  wherein C ring is optionally substituted 5- or 6-membered heterocyclewhich contains one or two hetero atoms, W³ represents a bond when C ringis 5-membered heterocycle, X and X′ are each independently —O—, —CH₂—,—NR¹— (wherein R¹ is hydrogen, optionally substituted lower alkyl, loweralkenyl, lower alkylcarbonyl or optionally substituted loweralkoxycarbonyl) or —S(O)p— wherein p is an integer of 0 to 2, Y and Y′are each independently optionally substituted lower alkyl, optionallysubstituted lower alkenyl, optionally substituted lower alkynyl,optionally substituted RC(O) wherein R is hydrogen, alkyl, alkenyl,cycloalkyl or aryl, optionally substituted cycloalkyl, optionallysubstituted cycloalkenyl, optionally substituted lower alkoxycarbonyl,optionally substituted amino, optionally substituted sulfamoyl,optionally substituted aryl or optionally substituted 5- or 6-memberedheterocycle, R¹, taken together with Y or Y′, may form —(CH₂)m—,—(CH₂)₂—Q—(CH₂)₂— (wherein Q is CH₂, O, S or NR′), —CR′═CH—CH═CR′—,—CH═N—CH═CH—, —N═CH—N═CH—, —C(═O)—O(CH₂)n—, —C(═O) —NR′—(CH₂)n— or—C(═O)—NR′—N═CH— wherein m is 4 or 5, n is 2 or 3, R′ is hydrogen, loweralkyl or lower alkenyl, Y may be optionally substituted lower alkoxywhen X is —CH₂—, Y′ may be optionally substituted lower alkoxy when XIis —CH₂—, Y may be optionally substituted lower alkoxycarbonyl,optionally substituted lower alkylsulfonyl or optionally substitutedarylsulfonyl when X is —O— or —NR¹—, Y′ may be optionally substitutedlower alkoxycarbonyl, optionally substituted lower alkylsulfonyl oroptionally substituted arylsulfonyl when X′ is —O— or —NR¹—, Y may behydrogen or halogen when X is —CH₂— or —NR¹—, Y′ may be hydrogen orhalogen when X′ is —CH₂— or —NR¹—, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰ and R¹¹are each independently hydrogen, halogen, hydroxy, optionallysubstituted lower alkyl, optionally substituted lower alkoxy, optionallysubstituted lower alkenyl, optionally substituted lower alkenyloxy,optionally substituted cycloalkyloxy, optionally substituted RC(O)—Owherein R is hydrogen, alkyl, cycloalkyl or aryl, carboxy, optionallysubstituted lower alkoxycarbonyl, optionally substituted loweralkenyloxycarbonyl, optionally substituted lower alkylthio, optionallysubstituted lower alkenylthio, optionally substituted amino, optionallysubstituted carbamoyl, guanidino, nitro, optionally substituted loweralkylsulfonyl, optionally substituted lower alkylsulfonyloxy, optionallysubstituted arylsulfonyl or optionally substituted arylsulfonyloxy,excluding (i) a compound wherein all of R⁸, R⁹, R¹⁰ and R¹¹ are selectedfrom hydrogen and halogen, (ii) a compound wherein C ring is optionallysubstituted pyrimidine ring, and at least one of —X—Y and —X′—Y′ isunsubstituted lower alkyl, unsubstituted lower alkoxy, unsubstitutedalkanoyloxy or unsubstituted lower alkylamino, and (iii) a compoundwherein one of A ring and C ring is substituted with optionallysubstituted phenylaminocarbonyl or optionally substituted benzoylamino,salt or hydrate thereof.
 14. The compound as claimed in claim 13 whereinR⁴ and R⁵ are each independently hydrogen, halogen or lower alkoxy, saltor hydrate thereof.
 15. The compound as claimed in clam 13 wherein oneof R⁴ and R5 is hydrogen and the other is halogen, salt or hydratethereof.
 16. The compound as claimed in any one of claims 13 to 15wherein both of R6 and R7 are hydrogen, salt or hydrate thereof.
 17. Thecompound as claimed in claim 17 wherein R⁸ and R¹¹ are eachindependently optionally substituted lower alkyl or optionallysubstituted lower alkoxy, salt or hydrate thereof.
 18. The compound asclaimed in claim 13 wherein R⁸ and R¹¹ are each independently methyl ormethoxy, salt or hydrate thereof.
 19. The compound as claimed in any oneof claims 13, 17 and 18 wherein R⁹ and R¹⁰ are each independentlyhydrogen or optionally substituted lower alkyl, salt or hydrate thereof.20. The compound as claimed in claim 13 wherein both of R⁸ and R¹¹ areoptionally substituted lower alkyl or both of R⁸ and R¹¹ are optionallysubstituted lower alkoxy, and both of R⁹ and R¹⁰ are simultaneouslyhydrogen or both of R⁹ and R¹⁰ are optionally substituted lower alkyl,salt or hydrate thereof.
 21. The compound as claimed in any one ofclaims 13, 15 and 20 wherein C ring is 5- or 6-membered heterocyclewhich contains at least one N atoms, salt or hydrate thereof.
 22. Thecompound as claimed in any one of claims 13, 15 and 20 wherein C ring is6-membered heterocycle which contains at least one N atom, salt orhydrate thereof.
 23. The compound as claimed in any one of claims 13, 15and 20 wherein C ring is optionally substituted pyridine or optionallysubstituted pyrimidine, salt or hydrate thereof.
 24. A compound of theformula (Ia′):

  wherein B ring is optionally substituted 5- or 6-membered ring whichcontains one or two hetero atoms (wherein the substituent is halogen,hydroxy, optionally substituted lower alkyl, optionally substitutedlower alkoxy, optionally substituted lower alkenyl, optionallysubstituted lower alkenyloxy, optionally substituted acyloxy, carboxy,optionally substituted lower alkoxycarbonyl, optionally substitutedlower alkenyloxycarbonyl, optionally substituted alkylthio, optionallysubstituted lower alkenylthio, optionally substituted amino, guanidino,nitro, optionally substituted lower alkylsulfonyl, optionallysubstituted lower alkylsulfonyloxy, optionally substituted arylsulfonylor optionally substituted arylsulfonyloxy, excluding a compound whereinB ring is substituted with only halogen(s)), and W² represents a bondwhen B ring is 5-membered heterocycle, X and X′ are each independently—O—, —CH₂—, —NR¹— (wherein R¹ is hydrogen, optionally substituted loweralkyl, lower alkenyl, lower alkylcarbonyl or optionally substitutedlower alkoxycarbonyl) or —S(O)p— wherein p is an integer of 0 to 2, Yand Y′ are each independently optionally substituted lower alkyl,optionally substituted lower alkenyl, optionally substituted loweralkynyl, optionally substituted RC(O) wherein R is hydrogen, alkyl,alkenyl, cycloalkyl or aryl, optionally substituted cycloalkyl,optionally substituted cycloalkenyl, optionally substituted loweralkoxycarbonyl, optionally substituted amino, optionally substitutedsulfamoyl, optionally substituted aryl or optionally substituted 5- or6-membered heterocycle, R¹, taken together with Y or Y′, may form—(CH₂)m, —(CH₂)₂—Q—(CH₂)₂— (wherein Q is CH₂, O, S or NR′),—CR′═CH—CH═CR′—, —CH═N—CH═CH—, —N═CH—N═CH—, —C(═O)—O(CH₂)n—,—C(═O)—NR′—(CH₂)n— or —C(═O)—NR′—N═CH— wherein m is 4 or 5, n is 2 or 3,R′ is hydrogen, lower alkyl or lower alkenyl, Y may be optionallysubstituted lower alkoxy when X is —CH₂—, Y′ may be optionallysubstituted lower alkoxy when X′ is —CH₂—, Y may be optionallysubstituted lower alkoxycarbonyl, optionally substituted loweralkylsulfonyl or optionally substituted arylsulfonyl when X is —O— or—NR¹—, Y′ may be optionally substituted lower alkoxycarbonyl, optionallysubstituted lower alkylsulfonyl or optionally substituted arylsulfonylwhen X′ is —O— or —NR¹—, Y may be hydrogen or halogen when X is —CH₂— or—NR¹, Y′ may be hydrogen or halogen when X′ is —CH₂— or —NR¹—, R⁴, R⁵,R⁶, R⁷, R¹², R¹³, R¹⁴ and R¹⁵ are each independently hydrogen, halogen,hydroxy, optionally substituted lower alkyl, optionally substitutedlower alkoxy, optionally substituted lower alkenyl, optionallysubstituted lower alkenyloxy, optionally substituted acyloxy, carboxy,optionally substituted lower alkoxycarbonyl, optionally substitutedlower alkenyloxycarbonyl, optionally substituted lower alkylthio,optionally substituted lower alkenylthio, optionally substituted amino,optionally substituted carbamoyl, guanidino, nitro, optionallysubstituted lower alkylsulfonyl, optionally substituted loweralkylsulfonyloxy, optionally substituted arylsulfonyl or optionallysubstituted arylsulfonyloxy, excluding (i) a compound wherein Y and Y′are simultaneously hydrogen, (ii) a compound wherein at least one of Yand Y′ is optionally substituted acyl, (iii) a compound wherein at leastone of —X—Y and —X′—Y′ is unsubstituted lower alkoxy, and (iv) acompound wherein —X—Y and —X′—Y′ are simultaneously optionallysubstituted lower alkoxy or amino substituted with phenyl, salt orhydrate thereof.
 25. The compound as claimed in claim 24 wherein R⁴ andR⁵ are ach independently hydrogen, halogen or lower alkyl, salt orhydrate thereof.
 26. The compound as claimed in claim 24 wherein one ofR⁴ and R⁵ is hydrogen and the other is halogen, salt or hydrate thereof.27. The compound as claimed in claim 24 or 26 wherein both of R⁶ band R⁷are hydrogen, salt or hydrate thereof.
 28. The compound as claimed inclaim 24 or 26 wherein B ring is 5- or 6-membered heterocycle whichcontains at least one N atom, salt or hydrate thereof.
 29. The compoundas claimed in claim 24 or 26 wherein B ring is 6-membered heterocyclewhich contains at least one N atom, salt or hydrate thereof.
 30. Thecompound as claimed in claim 24 or 26 wherein B ring is optionallysubstituted pyridine or optionally substituted pyrimidine, salt orhydrate thereof.
 31. The compound as claimed in claim 24 or 26 whereinR¹², R¹³, R¹⁴ and R¹⁵ are each independently hydrogen, halogen or loweralkyl, salt or hydrate threof.
 32. The compound as claimed in claim 13or 24 wherein one of X and X′ is —O— and the other is —NR¹— wherein R¹is hydrogen, optionally substituted lower alkyl, lower alkenyl, loweralkylcarbonyl or optionally substituted lower alkoxycarbonyl, salt orhydrate thereof.
 33. The compound as claimed in claim 13 or 24 whereinone of X and X′ is —O— and the other is —NR¹— wherein R¹ is hydrogen,lower alkyl or lower alkenyl and Y and Y′ are each independentlyoptionally substituted lower alkyl or optionally substituted loweralkenyl, salt or hydrate thereof.
 34. The compound as claimed in claim32 wherein R¹ is hydrogen, salt or hydrate thereof.
 35. The compound asclaimed in claim 13 or 24 wherein one of —X—Y and —X′—Y′ is optionallysubstituted lower alkylamino or optionally substituted loweralkenylamino and the other is optionally substituted lower alkoxy oroptionally substituted lower alkenyloxy, salt or hydrate thereof. 36.The compound as claimed in claim 13 or 24 wherein one of —X—Y and —X′—Y′is optionally substituted lower alkylamino or optionally substitutedlower alkenylamino and the other is prenyloxy, salt or hydrate thereof.37. The compound as claimed in claim 13 wherein R⁴, R⁵, R⁶ and R⁷ areeach independently hydrogen, halogen or lower alkyl, R⁸ and R¹¹ are eachindependently hydrogen, halogen, optionally substituted lower alkyl,optionally substituted lower alkoxy or lower alkoxycarbonyl, R⁹ and R¹⁰are each independently hydrogen, optionally substituted lower alkyl oroptionally substituted lower alkoxy, one of X and X′ is —O— and theother is —NR¹— wherein R¹ is hydrogen, lower alkyl, lower alkenyl orlower alkylcarbonyl, Y and Y′ are each independently optionallysubstituted lower alkyl, optionally substituted lower alkenyl oroptionally substituted lower alkynyl, and C ring is optionallysubstituted pyridine or optionally substituted pyrimidine, salt orhydrate thereof.
 38. The compound as claimed in claim 13 wherein X′ is—O—, —NR¹— or —S(O)p— and C ring is optionally substituted 5-memberedheteorcycle which contains one or two hetero atoms, salt or hydratethereof.
 39. The compound as claimed in claim 24 wherein R⁴, R⁵, R⁶ andR⁷ are each independently hydrogen, halogen or lower alkyl, R¹², R¹³,R¹⁴ and R¹⁵ are each independently hydrogen, halogen or lower alkyl, Bring is optionally substituted pyridine or optionally substitutedpyrimidine wherein the substituent is optionally substituted lower alkylor optionally substituted lower alkoxy, one of X and X′ is —O— and theother is —NR¹— wherein R¹ is hydrogen, lower alkyl, lower alkenyl orlower alkylcarbonyl and Y and Y′ are each independently optionallysubstituted lower alkyl, optionally substituted lower alkenyl oroptionally substituted lower alkynyl, salt or hydrate thereof.
 40. Acompound of the formula (If′):

  wherein one of B ring and C ring is optionally substituted 5- or6-membered heterocycle which contains one or two hetero atoms and theother is 6-membered heterocycle which contains at least one N atom,excluding a compound wherein every substituent of B ring is selectedfrom cyano and halogen, X and X′ are each independently —O—, —CH₂—,—NR¹— (wherein R¹ is hydrogen, optionally substituted lower alkyl, loweralkenyl, lower alkylcarbonyl or optionally substituted loweralkoxycarbonyl) or —S(O)p— wherein p is an integer of 0 to 2, Y and Y′are each independently optionally substituted lower alkyl, optionallysubstituted lower alkenyl, optionally substituted lower alkynyl,optionally substituted RC(O) wherein R is hydrogen, alkyl, alkenyl,cycloalkyl or aryl, optionally substituted cycloalkyl, optionallysubstituted cycloalkenyl, optionally substituted lower alkoxycarbonyl,optionally substituted amino, optionally substituted sulfamoyl,optionally substituted aryl or optionally substituted 5- or 6-memberedheterocycle, W²represents a bond when B ring is 5-membered heterocycle,and W³ represents a bond when C ring is 5-membered heterocycle, R¹,taken together with Y or Y′, may form —(CH₂)m—, —C(CH₂)₂—Q—(CH₂)₂—(wherein Q is CH₂, O, S or NR′), —CR′═CH—CH═CR′—, —CH═N—CH═CH—,—N═CH—N═CH—, —C(═O)—O(CH₂)n—, —C(═O)—NR′—(CH₂)n— or —C(═O)—NR′—N═CH—wherein m is 4 or 5, n is 2 or 3, R′ is hydrogen, lower alkyl or loweralkenyl, Y may be optionally substituted lower alkoxy when X is —CH₂—,Y′ may be optionally substituted lower alkoxy when X′ is —CH₂—, Y may beoptionally substituted lower alkoxycarbonyl, optionally substitutedlower alkylsulfonyl or optionally substituted arylsulfonyl when X is —O—or —NR¹—, Y′ may be optionally substituted lower alkoxycarbonyl,optionally substituted lower alkylsulfonyl or optionally substitutedarylsulfonyl when X′ is —O— or —NR¹, Y may be hydrogen or halogen when Xis —CH₂— or —NR¹, Y′ may be hydrogen or halogen when X′ is —CH₂— or—NR¹—, R⁴, R⁵, R⁶ and R⁷ are each independently hydrogen, halogen,hydroxy, optionally substituted lower alkyl, optionally substitutedlower alkoxy, optionally substituted lower alkenyl, optionallysubstituted lower alkenyloxy, optionally substituted cycloalkyloxy,optionally substituted RC(O)—O wherein R is hydrogen, alkyl, cycloalkylor aryl, carboxy, optionally substituted lower alkoxycarbonyl,optionally substituted lower alkenyloxycarbonyl, optionally substitutedlower alkylthio, optionally substituted lower alkenylthio, optionallysubstituted amino, optionally substituted carbamoyl, guanidino, nitro,optionally substituted lower alkylsulfonyl, optionally substituted loweralkylsulfonyloxy, optionally substituted arylsulfonyl or optionallysubstituted arylsulfonyloxy, salt or hydrate thereof.
 41. A compound ofthe formula (Ig′):

wherein A ring and C ring are each independently optionally substituted5- or 6-membered which contains one or two hetero atoms, W¹ represents abond when A ring is 5-membered heterocycle, W³ represents a bond when Cring is 5-membered heterocycle, X and X′ are each independently —O—,—CH₂—, —NR¹— (wherein R¹ is hydrogen, optionally substituted loweralkyl, lower alkenyl, lower alkylcarbonyl or optionally substitutedlower alkoxycarbonyl) or —S(O)p— wherein p is an integer of 0 to 2, Yand Y′ are each independently optionally substituted lower alkyl,optionally substituted lower alkenyl, optionally substituted loweralkynyl, optionally substituted RC(O) wherein R is hydrogen, alkyl,alkenyl, cycloalkyl or aryl, optionally substituted cycloalkyl,optionally substituted cycloalkenyl, optionally substituted loweralkoxycarbonyl, optionally substituted amino, optionally substitutedsulfamoyl, optionally substituted aryl or optionally substituted 5- or6-membered heterocycle, R¹, taken together with Y or Y′, may form—(CH₂)m—, —C(CH₂)₂—Q—(CH₂)₂— (wherein Q is CH₂, O, S or NR′),—CR′═CH—CH═CR′—, —CH═N—CH═CH—, —N═CH—N═CH—, —C(═O)—O(CH₂)n—,—C(═O)—NR′—(CH₂)n— or —C(═O)—NR′—N═CH— wherein m is 4 or 5, n is 2 or 3,and R′ is hydrogen, lower alkyl or lower alkenyl, Y may be optionallysubstituted lower alkoxy when X is —CH₂—, Y′ may be optionallysubstituted lower alkoxy when X′ is —CH₂—, Y may be optionallysubstituted lower alkoxycarbonyl, optionally substituted loweralkylsulfonyl or optionally substituted arylsulfonyl when X is —O— or—NR¹—, Y′ may be optionally substituted lower alkoxycarbonyl, optionallysubstituted lower alkylsulfonyl or optionally substituted arylsulfonylwhen X′ is —O— or —NR¹—, Y may be hydrogen or halogen when X is —NR¹—,Y′ may be hydrogen or halogen when X′ is —NR¹—, R⁸, R⁹, R¹⁰ and R¹¹ areeach independently hydrogen, halogen, hydroxy, optionally substitutedlower alkyl, optionally substituted lower alkoxy, optionally substitutedlower alkenyl, optionally substituted lower alkenyloxy, optionallysubstituted cycloalkyloxy, optionally substituted RC(O)—O wherein R ishydrogen, alkyl, cycloalkyl or aryl, carboxy, optionally substitutedlower alkoxycarbonyl, optionally substituted lower alkenyloxycarbonyl,optionally substituted lower alkylthio, optionally substituted loweralkenylthio, optionally substituted amino, optionally substitutedcarbamoyl, guanidino, nitro, optionally substituted lower alkylsulfonyl,optionally substituted lower alkylsulfonyloxy, optionally substitutedarylsulfonyl or optionally substituted arylsulfonyloxy, excluding acompound wherein all of R⁸, R⁹, R¹⁰ and R¹¹ are selected from hydrogenand halogen, salt or hydrate thereof.
 42. A pharmaceutical compositionfor use as an immunosuppressant comprising a compound of the formula(Ib′):

  wherein C ring is optionally substituted 5- or 6-membered heterocyclewhich contains one or two hetero atoms, W³ represents a bond when C ringis 5-membered heterocycle, X and X′ are each independently —O—, —CH₂—,—NR¹— (wherein R¹ is hydrogen, optionally substituted lower alkyl, loweralkenyl, lower alkylcarbonyl or optionally substituted loweralkoxycarbonyl), —S(O)_(p)— (wherein p is an integer of 0 to 2) or asingle bond, Y and Y′ are each independently optionally substitutedlower alkyl, optionally substituted lower alkenyl, optionallysubstituted lower alkynyl, optionally substituted RC(O) wherein R ishydrogen, alkyl, alkenyl, cycloalkyl or aryl, optionally substitutedcycloalkyl, optionally substituted cycloalkenyl, optionally substitutedlower alkoxycarbonyl, optionally substituted amino, optionallysubstituted sulfamoyl, optionally substituted aryl or optionallysubstituted 5- or 6-membered heterocycle, R¹, taken together with Y orY′, may form —(CH₂)m—, —C(CH₂)₂—Q—(CH₂)₂— (wherein Q is CH₂, O, S orNR′), —CR′═CH—CH═CR′—, —CH═N—CH═CH—, —N═CH—N═CH—, —C(═O)—O(CH₂)n—,—C(═O) —NR′—(CH₂)n— or —C(═O)—NR′—N═CH— wherein m is 4 or 5, n is 2 or3, and R¹ is hydrogen, lower alkyl or lower alkenyl, Y may be optionallysubstituted lower alkoxy when X is —CH₂—, Y′ may be optionallysubstituted lower alkoxy when X′ is —CH₂—, Y may be optionallysubstituted lower alkoxycarbonyl, optionally substituted loweralkylsulfonyl or optionally substituted arylsulfonyl when X is —O— or—NR¹—, Y′ may be optionally substituted lower alkoxycarbonyl, optionallysubstituted lower alkylsulfonyl or optionally substituted arylsulfonylwhen X′ is —O— or —NR¹—, Y may be hydrogen or halogen when X is —CH₂— or—NR¹—, Y′ may be hydrogen or halogen when X′ is —CH₂— or NR¹—, Y′ may behydrogen, hydroxy, halogen, nitro or oxo when X′ is a single bond, R⁴,R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰ and R¹¹ are each independently hydrogen,halogen, hydroxy, optionally substituted lower alkyl, optionallysubstituted lower alkoxy, optionally substituted lower alkenyl,optionally substituted lower alkenyloxy, optionally substitutedcycloalkyloxy, optionally substituted RC(O)—O wherein R is hydrogen,alkyl, cycloalkyl or aryl, carboxy, optionally substituted loweralkoxycarbonyl, optionally substituted lower alkenyloxycarbonyl,optionally substituted lower alkylthio, optionally substituted loweralkenylthio, optionally substituted amino, optionally substitutedcarbamoyl, guanidino, nitro, optionally substituted lower alkylsulfonyl,optionally substituted lower alkylsulfonyloxy, optionally substitutedarylsulfonyl or optionally substituted arylsulfonyloxy, excluding acompound wherein all of R⁸, R⁹, R¹⁰ and R¹¹ are selected from hydrogenand halogen, salt or hydrate thereof.
 43. A pharmaceutical compositionfor use as an immunosuppressant comprising a compound of the formula(Ia′):

  wherein B ring is optionally substituted 5- or 6- membered heterocyclewhich contains one or two hetero atoms excluding a compound whereinevery substituent of B ring is selected from cyano and halogen, W²represents a bond when B ring is 5-membered heterocycle, X and X′ areeach independently —O—, —CH₂—, —NR¹— (wherein R¹ is hydrogen, optionallysubstituted lower alkyl, lower alkenyl, lower alkylcarbonyl oroptionally substituted lower alkoxycarbonyl) or —S(O)p— wherein p is aninteger of 0 to 2, Y and Y′ are each independently optionallysubstituted lower alkyl, optionally substituted lower alkenyl,optionally substituted lower alkynyl, optionally substituted RC(O)wherein R is hydrogen, alkyl, alkenyl, cycloalkyl or aryl, optionallysubstituted cycloalkyl, optionally substituted cycloalkenyl, optionallysubstituted lower alkoxycarbonyl, optionally substituted amino,optionally substituted sulfamoyl, optionally substituted aryl oroptionally substituted 5- or 6-membered heterocycle, R¹, taken togetherwith Y or Y′, may form —(CH₂)m—, —C(CH₂)₂—Q—(CH₂)₂— (wherein Q is CH₂,O, S or NR′), —CR′═CH—CH═CR′—, —CH═N—CH═CH—, —N═CH—N═CH—,—C(═O)—O(CH₂)n—, —C(═O)—NR′—(CH₂)n— or —C(═O)—NR′—N═CH— wherein m is 4or 5, n is 2 or 3, R′ is hydrogen, lower alkyl or lower alkenyl, Y maybe optionally substituted lower alkoxy when X is —CH₂—, Y′ may beoptionally substituted lower alkoxy when X′ is —CH₂—, Y may beoptionally substituted lower alkoxycarbonyl, optionally substitutedlower alkylsulfonyl or optionally substituted arylsulfonyl when X is —O—or —NR¹—, Y′ may be optionally substituted lower alkoxycarbonyl,optionally substituted lower alkylsulfonyl or optionally substitutedarylsulfonyl when X′ is —O— or, —NR¹—, Y may be hydrogen or halogen whenX is —CH₂— or —NR¹—, Y′ may be hydrogen or halogen when X′ is —CH₂— or—NR¹—, R⁴, R⁵, R⁶, R¹², R¹³, R¹⁴ and R¹⁵ are each independentlyhydrogen, halogen, hydroxy, optionally substituted lower alkyl,optionally substituted lower alkoxy, optionally substituted loweralkenyl, optionally substituted lower alkenyloxy, optionally substitutedcycloalkyloxy, optionally substituted RC(O)—O wherein R is hydrogen,alkyl, cycloalkyl or aryl, carboxy, optionally substituted loweralkoxycarbonyl, optionally substituted lower alkenyloxycarbonyl,optionally substituted lower alkylthio, optionally substituted loweralkenylthio, optionally substituted amino, optionally substitutedcarbamoyl, guanidino, nitro, optionally substituted lower alkylsulfonyl,optionally substituted lower alkylsulfonyloxy, optionally substitutedarylsulfonyl or optionally substituted arylsulfonyloxy, excluding (i) acompound wherein —X—Y and X′—Y′ are simultaneously unsubstituted loweralkyl, optionally substituted lower alkoxy or unsubstituted acyloxy,(ii) a compound wherein one of —X—Y and —X′—Y′ is methyl and the otheris methoxy, and (iii) a compound wherein —X′—Y′ is hydrogen or halogenand —X—Y is unsubstituted lower alkyl, unsubstituted lower alkoxy ordi(lower) alkylamino, salt or hydrate thereof.
 44. A pharmaceuticalcomposition comprising the compound of the formula (If′), salt orhydrate thereof according to claim 40 and a pharmaceutically acceptablecarrier.
 45. A pharmaceutical composition comprising the compound of theformula (Ig′), salt or hydrate thereof according to claim 41 and apharmaceutically acceptable carrier.
 46. A pharmaceutical compositioncomprising the compound of the formula (If′) according to claim 40, thecompound of the formula (Ig′) according to claim 41, the compound of theformula (Ib′) according to claim 42, the compound of the formula (Ia′)according to claim 43, salt or hydrate thereof according to claim 41 anda pharmaceutically acceptable carrier.
 47. A method for suppressing IgEproduction in a human in need thereof comprising administering thecompound of the formula (If′) according to claim 40, the compound of theformula (Ig′) according to claim 41, the compound of the formula (Ib′)according to claim 42, the compound of the formula (Ia′) according toclaim 43, salt or hydrate thereof according to claim 41 and apharmaceutically acceptable carrier to said human, wherein a combinationof said compounds suppresses IgE production in said human.
 48. A methodfor suppressing an immune response, comprising administering thecompound of the formula (If′) according to claim 40, the compound of theformula (Ig′) according to claim 41, the compound of the formula (Ib′)according to claim 42, the compound of the formula (Ia′) according toclaim 43, salt or hydrate thereof.
 49. A method for treating allergicdiseases, comprising administering the compound of the formula (If′)according to claim 40, the compound of the formula (Ig′) according toclaim 41, the compound of the formula (Ib′) according to claim 42, thecompound of the formula (Ia′) according to claim 43, salt or hydratethereof and a pharmaceutically acceptable carrier to said human, whereina combination of said compounds suppresses immune response or treatsallergic diseases in said human.
 50. A compound of the formula:

  wherein R⁴ and R⁵ are each independently hydrogen, halogen or loweralkoxy, R⁶ and R⁷ are each independently hydrogen, halogen or loweralkyl, both of R⁸ and R¹¹ are lower alkyl or one of R⁸ and R¹¹ is loweralkyl and the other is lower alkoxy, both of R⁹ and R¹⁰ are hydrogen orboth of R⁹ and R¹⁰ are lower alkyl, one of —X—Y and —X′—Y′ is optionallysubstituted lower alkylamino or optionally substituted loweralkenylamino and the other is prenyloxy, salt or hydrate thereof.
 51. Acompound of the formula:

  wherein

  and —X′—Y′ is the same as defined in claim 13, salt or hydratethereof.
 52. The compound as claimed in claim 33, wherein R¹ ishydrogen, salt or hydrate thereof.
 53. The compound according to claim1, 13, or 24, wherein a substituent of said optionally substituted loweralkyl is selected from the group consisting of: halogen; hydroxy; loweralkoxy optionally substituted with lower alkoxy; acyl; acyloxy; carboxy;lower alkoxycarbonyl; mercapt; lower alkylthio; amino optionallysubstituted with hydroxy, lower alkyl or optionally substituted acyl;imino optionally substituted with hydroxy, lower alkoxy,carboxy(lower)alkoxy, aryl(lower)alkoxy or 5- or 6-membered heterocycle;hydrazono optionally substituted with carbamoyl or lower alkoxycarbonyl;carbamoyl optionally substituted with lower alkyl or amino;thiocarbamoyl optionally substituted with lower alkyl; cycloalkyloptionally substituted with lower alkyl or lower alkoxy; cycloalkenyloptionally substituted with lower alkyl; cyano; phenyl optionallysubstituted with at least one substituent selected from the group ofhydroxy, lower alkyl, carboxy, lower alkoxycarbonyl and lower alkoxy;and 5- or 6-membered heterocycle which may be substituted with loweralkyl and may fuse with benzene ring.
 54. The compound according toclaim 1, 13, or 24, wherein a substituent for said optionallysubstituted lower alkoxy is selected from the group consisting of:halogen; hydroxy; lower alkoxy optionally substituted with acyloxy;acyl; acyloxy optionally substituted with hydroxy or carboxy; carboxy;lower alkoxycarbonyl; lower alkylthio; amino optionally substituted withlower alkyl; phenyl optionally substituted with lower alkyl or loweralkoxy; heterocycle; and heterocyclylcarbonyloxy.
 55. The compoundaccording to claim 1, 13, or 24, wherein a substituent of saidoptionally substituted lower alkoxycarbonyl, optionally substitutedlower alkylsulfonyl, optionally substituted alkylsulfonyloxy, optionallysubstituted lower alkylthio, optionally substituted lower alkylamino, oroptionally substituted lower alkylenedioxy is selected from the groupconsisting of: halogen; hydroxy; lower alkoxy optionally substitutedwith lower alkoxy; acyl; acyloxy; carboxy; lower alkoxycarbonyl;mercapt; lower alkylthio; amino optionally substituted with hydroxy,lower alkyl or optionally substituted acyl; imino optionally substitutedwith hydroxy, lower alkoxy, carboxy(lower)alkoxy, aryl(lower)alkoxy or5- or 6-membered heterocycle; hydrazono optionally substituted withcarbamoyl or lower alkoxycarbonyl; carbamoyl optionally substituted withlower alkyl or amino; thiocarbamoyl optionally substituted with loweralkyl; cycloalkyl optionally substituted with lower alkyl or loweralkoxy; cycloalkenyl optionally substituted with lower alkyl; cyano;phenyl optionally substituted with at least one substituent selectedfrom the group of hydroxy, lower alkyl, carboxy, lower alkoxycarbonyland lower alkoxy; and 5- or 6-membered heterocycle which may besubstituted with lower alkyl and may fuse with benzene ring.
 56. Thecompound according to claim 1, 13, or 24, wherein a substituent of saidoptionally substituted lower alkoxycarbonyl, said optionally substitutedlower alkylsulfonyl, or said optionally substituted lower alkylthio isselected from the group consisting of: halogen; hydroxy; lower alkoxyoptionally substituted with acyloxy; acyl; acyloxy optionallysubstituted with hydroxy or carboxy; carboxy; lower alkoxycarbonyl;lower alkylthio; amino optionally substituted with lower alkyl; phenyloptionally substituted with lower alkyl.
 57. The compound according toclaim 1, 13, or 24, wherein a substituent of said optionally substitutedlower alkenyl is selected from the group consisting of: halogen;hydroxy; lower alkoxy optionally substituted with acyloxy; acyl; acyloxyoptionally substituted with hydroxy or carboxy; carboxy; loweralkoxycarbonyl; lower alkylthio; amino optionally substituted with loweralkyl; phenyl optionally substituted with lower alkyl or lower alkoxy;heterocycle; and heterocyclylcarbonyloxy.
 58. The compound according toclaim 1, 13, or 24, wherein a substituent for said optionallysubstituted lower alkenyloxy, said optionally substituted loweralkenyloxycarbonyl, or said optionally substituted lower alkenylthio isselected from the group consisting of: halogen; hydroxy; lower alkoxyoptionally substituted with acyloxy; acyl; acyloxy optionallysubstituted with hydroxy or carboxy; carboxy; lower alkoxycarbonyl;lower alkylthio; amino optionally substituted with lower alkyl; phenyloptionally substituted with lower alkyl or lower alkoxy; heterocycle;and heterocyclylcarbonyloxy.
 59. The compound according to claim 1, 13,or 24, wherein a substituent for said optionally substituted loweralkynyl is selected from the group consisting of: halogen; hydroxy;lower alkoxy optionally substituted with acyloxy; acyl; acyloxyoptionally substituted with hydroxy or carboxy; carboxy; loweralkoxycarbonyl; lower alkylthio; amino optionally substituted with loweralkyl; phenyl optionally substituted with lower alkyl or lower alkoxy;heterocycle; and heterocyclylcarbonyloxy.
 60. The compound according toclaim 1, 13, or 24, wherein a substituent for said optionallysubstituted lower acyl or said optionally substituted acyloxy isselected from the group consisting of: halogen; hydroxy; lower alkoxyoptionally substituted with acyloxy; acyl; acyloxy optionallysubstituted with hydroxy or carboxy; carboxy; lower alkoxycarbonyl;lower alkylthio; amino optionally substituted with lower alkyl; phenyloptionally substituted with lower alkyl or lower alkoxy; heterocycle;and heterocyclylcarbonyloxy.
 61. The compound according to claim 1, 13,or 24, wherein a substituent of said optionally substituted lowercycloalkyl, or said optionally substituted cycloalkenyl is selected fromthe group consisting of: lower alkyl, halogen, hydroxy, carboxy, loweralkoxycarbonyl, lower alkoxy, lower alkylenedioxy, imino optionallysubstituted with lower alkoxy, aryl, and 5- or 6-membered heterocycle.62. The compound according to claim 1, 13, or 24, wherein a substituentfor said optionally substituted lower amino is selected from the groupconsisting of: optionally substituted lower alkyl, wherein thesubstituents are lower alkoxy, cycloalkyl, optionally substituted amino(wherein the substituents are aroyl optionally substituted withacyloxy(lower)alkoxy), optionally substituted aryl (wherein thesubstituents are lower alkyl, lower alkoxy, carboxy or loweralkoxycarbonyl) or heterocycle; lower alkenyl; lower alkynyl;cycloalkyl; aryl optionally substituted with lower alkyl, carboxy, acyl,lower alkoxycarbonyl; sulfamoyl optionally substituted with lower alkyl;optionally substituted lower alkoxycarbonyl, wherein the substituentsare halogen, acyloxy, acyloxy substituted with hydroxy, acyloxysubstituted with carboxy or heterocyclylcarbonyloxy; and loweralkylsulfonyl.
 63. The compound according to claim 1, 13, or 24, whereina substituent of said optionally substituted carbamoyl is selected fromthe group consisting of: lower alkyl, lower alkenyl, and lower alkynyl.64. The compound according to claim 1, 13, or 24, wherein a substituentfor said optionally substituted sulfamoyl is selected from the groupconsisting of: lower alkyl, lower alkenyl, and lower alkynyl.
 65. Thecompound according to claim 1, 13, or 24, wherein a substituent for saidoptionally substituted aromatic carbocycle, said optionally substitutedaryl, or said optionally substituted arylsulfonyl is selected from thegroup consisting of: halogen; hydroxy; lower alkyl optionallysubstituted with halogen or carboxy; lower alkoxy optionally substitutedwith halogen, aryl, heteroaryl or lower alkoxy; lower alkenyl; loweralkynyl; cycloalkyl; lower alkenyloxy; lower alkynyloxy; cycloalkoxy;acyl; acyloxy; carboxy; lower alkoxycarbonyl; lower alkenyloxycarbonyl;lower alkylthio; lower alkynylthio; amino optionally substituted withlower alkyl, cycloalkyl(lower)alkyl, heteroaryl(lower)alkyl, loweralkenyl, cycloalkyl, acyl optionally substituted with halogen, loweralkoxycarbonyl, or lower alkylsulfonyl; guanidino; nitro; loweralkylsulfonyl; dihydroxyborane; lower alkylsulfonyloxy optionallysubstituted with halogen; arylsulfonyl; arylsulfonyloxy; aryl; and 5- or6-membered heterocycle.
 66. The compound according to claim 1, 13, or24, wherein said substituent of said optionally substituted 5- or6-membered heterocycle, said optionally substituted 5- or 6-memberedring which may fuse with benzene ring, or said optionally substituted 5-or 6-membered heterocycle which contains one or two of hetero atoms isselected from the group consisting of: halogen; hydroxy; lower alkyloptionally substituted with hydroxy or acyloxy; lower alkoxy optionallysubstituted with halogen, aryl or 5- or 6-membered heterocycle; loweralkenyl; lower alkenyloxy; lower alkynyl; lower alkynyloxy; acyloxy;carboxy; lower alkoxycarbonyl; mercapt; lower alkylthio; loweralkenylthio; amino which may be mono- or di-substituted with halogen,optionally substituted lower alkyl wherein the substituents arecycloalkyl or 5- or 6-membered heterocycle, acyl optionally substitutedwith halogen, lower alkenyl, cycloalkyl, or lower alkylsulfonyl; iminooptionally substituted with lower alkylsulfonyl; nitro; loweralkylsulfonyl; aryl; 5- or 6-membered heterocycle; oxo; and oxide.
 67. Acompound of the formula (I):

  wherein A ring and C ring are each independently optionallysubstituted aromatic carbocycle or optionally substituted 5- or6-membered heterocycle which may fuse with benzene ring, wherein 5- or6-membered heterocycle is pyrrole ring, imidazole ring, pyridine ring,pyridazine ring, pyrazine ring, triazole ring, triazine ring, isoxazolering, oxazolo ring, isothiazole ring, thiazole ring, thiadiazole ring,furan ring, thiophene ring, tetrahydropyrane ring, dihydropyridine ring,dihydropyridazine, dihydropyrazine ring, dioxane ring, oxathiorane ring,thiane ring, pyrrolidine ring, pyrroline ring, imidazolidine ring,imidazoline ring, pyrazolidine ring, pyrazoline ring, piperidine ring,piperazine ring or morpholine ring, B ring is optionally substitutedaromatic carbocycle or optionally substituted 5- or 6-memberedheterocycle which may fuse with benzene ring, wherein 5- or 6-memberedheterocycle is pyrazole ring, pyridine ring, pyridazine ring, pyrazinering, triazole ring, triazine ring, isoxazole ring, oxadiazole ring,isothiazole ring, thiadiazole ring, tetrahydropyrane ring,dihydropyridine ring, dihydropyridazine, dihydropyrazine ring, dioxanering, oxathiorane ring, thiane ring, pyrrolidine ring, pyrroline ring,imidazolidine ring, imidazoline ring, pyrazolidine ring, pyrazolinering, piperdine ring, piperzine ring, morpholine ring, W¹, W² and/or W³represents a single bond when A ring, B ring and/or C ring is optionallysubstituted 5-membered heterocycle, X is —O—, —CH₂—, —NR¹— wherein R¹ ishydrogen, optionally substituted lower alkyl, lower alkenyl, loweralkylcarbonyl or optionally substituted lower alkoxycarbonyl or —S(O)p—wherein p is an integer of 0 to 2, Y is hydrogen, optionally substitutedlower alkyl, optionally substituted lower alkenyl, optionallysubstituted lower alkynyl, optionally substituted RC(O) wherein R ishydrogen, alkyl, alkenyl, cycloalkyl or aryl, optionally substitutedcycloalkyl, optionally substituted cycloalkenyl, optionally substitutedlower alkoxycarbonyl, optionally substituted sulfamoyl, optionallysubstituted amino, optionally substituted aryl or optionally substituted5- or 6-membered heterocycle, Y may be optionally substituted loweralkoxy when X is —CH₂—, Y may be optionally substituted loweralkoxycarbonyl, optionally substituted lower alkylsulfonyl or optionallysubstituted arylsulfonyl when X is —O— or —NR¹—, one of V¹ and V² is asingle bond and the other is a single bond, an —O— bond, an —NH— bond,an —OCH₂— bond, a —CH₂O— bond, a —CH═CH— bond, a —C≡C— bond, a —CH(OR²)—bond, wherein R² is hydrogen or lower alkyl, a —CO— bond, or an —NHCHR³—bond, wherein R³ is hydrogen or hydroxy, and at least one of A ring, Bring and C ring is optionally substituted aromatic carbocycle and atleast another one is optionally substituted 5- or 6-membered heterocyclewhich may fuse with benzene ring when both of V¹ and V² are singlebonds, salt or hydrate thereof.
 68. A compound of the formula (I):

  wherein A ring is optionally substituted aromatic carbocycle oroptionally substituted- 5- or 6-membered heterocycle which may fuse withbenzene ring, wherein 5- or 6-membered heterocycle is pyrrole ring,imidazole ring, pyridine ring, pyridazine ring, pyrimidine ring,pyrazine ring, triazole ring, triazine ring, isoxazole ring, oxazolering, oxadiazole ring, isothiazole ring, thiazole ring, thiadiazolering, furan ring, thiophene ring, tetrahydropyrane ring, dihydropyridinering, dihydropyridazine, dihydropyrazine ring, dioxane ring, oxathioranering, thiane ring, pyrrolidine ring, pyrroline ring, imidazolidine ring,imidazoline ring, pyrazolidine ring, pyrazoline ring, piperidine ring,piperazine ring or morpholine ring, B ring is optionally substitutedaromatic carbocycle or optionally substituted 5- or 6-memberedheterocycle which may fuse with benzene ring, C ring is optionallysubstituted pyrazole ring, W¹, W² and/or W³ represents a single bondwhen A ring, B ring and/or C ring is optionally substituted 5-memberedheterocycle, X is —O—, —CH₂—, —NR¹— wherein R¹ is hydrogen, optionallysubstituted lower alkyl, lower alkenyl, lower alkylcarbonyl oroptionally substituted lower alkoxycarbonyl or —S(O)p— wherein p is aninteger of 0 to 2, Y is hydrogen, optionally substituted lower alkyl,optionally substituted lower alkenyl, optionally substituted loweralkynyl, optionally substituted RC(O) wherein R is hydrogen, alkyl,alkenyl, cycloalkyl or aryl, optionally substituted cycloalkyl,optionally substituted cycloalkenyl, optionally substituted loweralkoxycarbonyl, optionally substituted sulfamoyl, optionally substitutedamino, optionally substituted aryl or optionally substituted 5- or6-membered heterocycle, Y may be optionally substituted lower alkoxywhen X is —CH₂—, Y may be optionally substituted lower alkoxycarbonyl,optionally substituted lower alkylsulfonyl or optionally substitutedarylsulfonyl when X is —O— or —NR¹—, one of V¹ and V² is a single bondand the other is a single bond, an —O— bond, an —NH— bond, an —OCH₂—bond, a —CH₂O— bond, a —CH═CH— bond, a —C≡C— bond, a —CH(OR²)— bond,wherein R² is hydrogen or lower alkyl, a —CO— bond, or an —NHCHR³— bond,wherein R³ is hydrogen or hydroxy, and at least one of A ring, B ringand C ring is optionally substituted aromatic carbocycle and at leastanother one is optionally substituted 5- or 6-membered heterocycle whichmay fuse with benzene ring when both of V¹ and V² are single bonds, saltor hydrate thereof.
 69. A compound of the formula (I):

  wherein A ring and B ring are each independently optionallysubstituted aromatic carbocycle or optionally substituted 5- or6-membered heterocycle which may fuse with benzene ring, C ring isoptionally substituted pyrimidine ring, W¹ and/or W² represents a singlebond when A ring and/or B ring is optionally substituted 5-memberedheterocycle, X is —O—, —CH₂—, —NR¹— wherein R¹ is hydrogen, optionallysubstituted lower alkyl, lower alkenyl, lower alkylcarbonyl oroptionally substituted lower alkoxycarbonyl or —S(O)p— wherein p is aninteger of 0 to 2, Y is optionally substituted lower alkenyl, optionallysubstituted lower alkynyl, optionally substituted cycloalkyl optionallysubstituted cycloalkenyl, optionally substituted lower alkoxycarbonyl,optionally substituted sulfamoyl, optionally substituted amino,optionally substituted aryl or optionally substituted 5- or 6-memberedheterocycle, Y may be optionally substituted lower alkoxy when X is—CH₂—, Y may be optionally substituted lower alkoxycarbonyl, optionallysubstituted lower alkylsulfonyl or optionally substituted arylsulfonylwhen X is —O— or —NR¹—, Y may be optionally substituted RC(O) wherein Ris hydrogen, alkyl, alkenyl, cycloalkyl or aryl when X is —NR¹—, Y maybe hydrogen when X is —O— or —S(O)p—, one of V¹ and V² is a single bondand the other is a single bond, an —O— bond, an —NH— bond, an —OCH₂—bond, a —CH₂O— bond, a —CH═CH— bond, a —C≡C— bond, a —CH(OR²)— bond,wherein R² is hydrogen or lower alkyl, a —CO— bond, or an —NHCHR³— bond,wherein R³ is hydrogen or hydroxy, and at least one of A ring, B ringand C ring is optionally substituted aromatic carbocycle and at leastanother one is optionally substituted 5- or 6-membered heterocycle whichmay fuse with benzene ring when both of V¹ and V² are single bonds, saltor hydrate thereof.
 70. A compound of the formula (Ib′):

  wherein C ring is optionally substituted 5- or 6-membered heterocycle,W³ represents a bond when C ring is 5-membered heterocycle, wherein 5-or 6-heterocycle is pyrrole ring, imidazole ring, pyrazole ring,pyridine ring, pyridazine ring, pyrazine ring, isoxazole ring, oxazolering, isothiazole ring, thiazole ring, furan ring, thiophene ring,tetrahydropyrane ring, dihydropyridine ring, dihydropyridazine,dihydropyrazine ring, dioxane ring, oxathiorane ring, thiane ring,pyrrolidine ring, pyrroline ring, imidazolidine ring, imidazoline ring,pyrazolidine ring, pyrazoline ring, piperidine ring, piperazine ring ormorpholine ring, X and X′ are each independently —O—, —CH₂—, —NR¹—(wherein R¹ is hydrogen, optionally substituted lower alkyl, loweralkenyl, lower alkylcarbonyl or optionally substituted loweralkoxycarbonyl) or —S(O)p— wherein p is an integer of 0 to 2, Y and Y′are each independently optionally substituted lower alkyl, optionallysubstituted lower alkenyl, optionally substituted lower alkynyl,optionally substituted RC(O) wherein R is hydrogen, alkyl, alkenyl,cycloalkyl or aryl, optionally substituted cycloalkyl, optionallysubstituted cycloalkenyl, optionally substituted lower alkoxycarbonyl,optionally substituted amino, optionally substituted sulfamoyl,optionally substituted aryl or optionally substituted 5- or 6-memberedheterocycle, R¹, taken together with Y or Y′, may form —(CH₂)m—,—C(CH₂)₂—Q—(CH₂)₂— (wherein Q is CH₂, O, S or NR′), —CR′═CH—CH═CR′—,—CH═N—CH═CH—, —N═CH—N═CH—, —C(═O)—O(CH₂)n—, —C(═O)—NR′—(CH₂)n— or—C(═O)—NR′—N═CH— wherein m is 4 or 5, n is 2 or 3, R′ is hydrogen, loweralkyl or lower alkenyl, Y may be optionally substituted lower alkoxywhen X is —CH₂—, Y′ may be optionally substituted lower alkoxy when X′is —CH₂—, Y may be optionally substituted lower alkoxycarbonyl,optionally substituted lower alkylsulfonyl or optionally substitutedarylsulfonyl when X is —O— or —NR¹—, Y′ may be optionally substitutedlower alkoxycarbonyl, optionally substituted lower alkylsulfonyl oroptionally substituted arylsulfonyl when X′ is —O— or —NR¹—, Y may behydrogen or halogen when X is —CH₂— or —NR¹—, Y′ may be hydrogen orhalogen when X′ is —CH₂— or —NR¹—, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰ and R¹¹are each independently hydrogen, halogen, hydroxy, optionallysubstituted lower alkyl, optionally substituted lower alkoxy, optionallysubstituted lower alkenyl, optionally substituted lower alkenyloxy,optionally substituted cycloalkyloxy, optionally substituted RC(O)Owherein R is hydrogen, alkyl, alkenyl, cycloalkyl or aryl, carboxy,optionally substituted lower alkoxycarbonyl, optionally substitutedlower alkenyloxycarbonyl, optionally substituted lower alkylthio,optionally substituted lower alkenylthio, optionally substituted amino,optionally substituted carbamoyl, guanidino, nitro, optionallysubstituted lower alkylsulfonyl, optionally substituted loweralkylsulfonyloxy, optionally substituted arylsulfonyl or optionallysubstituted arylsulfonyloxy, excluding a compound wherein all of R⁸, R⁹,R¹⁰ and R¹¹ are selected from hydrogen and halogen, salt or hydratethereof.
 71. A compound of the formula (Ib′):

  wherein C ring is optionally substituted pyrimidine, X and X′ are eachindependently —O—, —CH₂—, —NR¹— (wherein R¹ is hydrogen, optionallysubstituted lower alkyl, lower alkenyl, lower alkylcarbonyl oroptionally substituted lower alkoxycarbonyl) or —S(O)p— wherein p is aninteger of 0 to 2, Y and Y′ are each independently optionallysubstituted lower alkenyl, optionally substituted lower alkynyl,optionally substituted cycloalkyl optionally substituted cycloalkenyl,optionally substituted lower alkoxycarbonyl, optionally substitutedamino, optionally substituted sulfamoyl, optionally substituted aryl oroptionally substituted 5- or 6-membered heterocycle, R¹, taken togetherwith Y or Y′, may form —(CH₂)m—, —C(CH₂)₂—Q—(CH₂)₂— (wherein Q is CH₂,O, S or NR′), —CR′═CH—CH═CR′—, —CH═N—CH═CH—, —N═CH—N═CH—,—C(═O)—O(CH₂)n—, —C(═O)—NR′—(CH₂)n— or —C(═O)—NR′—N═CH— wherein m is 4or 5, n is 2 or 3, R′ is hydrogen, lower alkyl or lower alkenyl, Y maybe optionally substituted lower alkoxy when X is —CH₂—, Y′ may beoptionally substituted lower alkoxy when X′ is —CH₂—, Y may beoptionally substituted lower alkoxycarbonyl, optionally substitutedlower alkylsulfonyl or optionally substituted arylsulfonyl when X is —O—or —NR¹—, Y′ may be optionally substituted lower alkoxycarbonyl,optionally substituted lower alkylsulfonyl or optionally substitutedarylsulfonyl when X′ is —O— or —NR¹—, Y may be halogen when X is —CH₂—or —NR¹—, Y′ may be halogen when X′ is —CH₂— or —NR¹—, Y may beoptionally substituted RC(O) wherein R is hydrogen, alkyl, alkenyl,cycloalkyl or aryl when X is —NR¹—, Y′ may be optionally substitutedRC(O) wherein R is hydrogen, alkyl, alkenyl, cycloalkyl or aryl when X′is —NR¹—, Y may be hydrogen when X is —NR¹—, Y′ may be hydrogen when X′is —NR¹—, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰ and R¹¹ are each independentlyhydrogen, halogen, hydroxy, optionally substituted lower alkyl,optionally substituted lower alkoxy, optionally substituted loweralkenyl, optionally substituted lower alkenyloxy, optionally substitutedcycloalkyloxy, optionally substituted RC(O)O wherein R is hydrogen,alkyl, alkenyl, cycloalkyl or aryl, carboxy, optionally substitutedlower alkoxycarbonyl, optionally substituted lower alkenyloxycarbonyl,optionally substituted lower alkylthio, optionally substituted loweralkenylthio, optionally substituted amino, optionally substitutedcarbamoyl, guanidino, nitro, optionally substituted lower alkylsulfonyl,optionally substituted lower alkylsulfonyloxy, optionally substitutedarylsulfonyl or optionally substituted arylsulfonyloxy, excluding acompound wherein all of R⁸, R⁹, R¹⁰ and R¹¹ are selected from hydrogenand halogen, salt or hydrate thereof.
 72. A compound of the formula(Ia′):

  wherein B ring is optionally substituted 5- or 6-membered heterocycle(wherein 5- or 6-heterocycle is pyrazole ring, pyridine ring, pyridazinering, pyrazine ring, isoxazole ring, isothiazole ring, tetrahydropyranering, thiane ring, pyrrolidine ring, pyrroline ring, imidazolidine ring,imidazoline ring, pyrazolidine ring, pyrazoline ring, piperidine ring,piperazine ring, morpholine ring, and the substituent is halogen,hydroxy, optionally substituted lower alkyl, optionally substitutedacyloxy, optionally substituted lower alkenyl, optionally substitutedlower alkenyloxy, optionally substituted RC(Q)Q wherein R is hydrogen,alkyl, alkenyl, cycloalkyl or aryl, carboxy, optionally substitutedlower alkoxycarbonyl, optionally substituted lower alkenyloxycarbonyl,optionally substituted alkylthio, optionally substituted loweralkenylthio, optionally substituted amino, guanidine, nitro, optionallysubstituted lower alkylsulfonyl, optionally substituted loweralkylsulfonyloxy, optionally substituted arylsulfonyl or optionallysubstituted arylsulfonyloxy, excluding a compound wherein B ring issubstituted with only halogen(s)), and W² represents a bond when B ringis 5-membered heterocycle, X and X′ are each independently —O—, —CH₂—,—NR¹— (wherein R¹ is hydrogen, optionally substituted lower alkyl, loweralkenyl, lower alkylcarbonyl or optionally substituted loweralkoxycarbonyl) or —S(O)p— wherein p is an integer of 0 to 2, Y and Y′are each independently optionally substituted lower alkyl, optionallysubstituted lower alkenyl, optionally substituted lower alkynyl,optionally substituted RC(O) wherein R is hydrogen, alkyl, alkenyl,cycloalkyl or aryl, optionally substituted cycloalkyl, optionallysubstituted cycloalkenyl, optionally substituted lower alkoxycarbonyl,optionally substituted amino, optionally substituted sulfamoyl,optionally substituted aryl or optionally substituted 5- or 6-memberedheterocycle, R¹, taken together with Y or Y′, may form —(CH₂)m,—C(CH₂)₂—Q—(CH₂)₂— (wherein Q is CH₂, O, S or NR′), —CR′═CH—CH═CR′—,—CH═N—CH═CH—, —N—CH—N═CH—, —C(═O)—O(CH₂)n—, —C(═O)—NR′—(CH₂)n— or—C(═O)—NR′—N═CH— wherein m is 4 or 5, n is 2 or 3, R′ is hydrogen, loweralkyl or lower alkenyl, Y may be optionally substituted lower alkoxywhen X is —CH₂—, Y′ may be optionally substituted lower alkoxy when X′is —CH₂—, Y may be optionally substituted lower alkoxycarbonyl,optionally substituted lower alkylsulfonyl or optionally substitutedarylsulfonyl when X is —O— or —NR¹—, Y′ may be optionally substitutedlower alkoxycarbonyl, optionally substituted lower alkylsulfonyl oroptionally substituted arylsulfonyl when X′ is —O— or —NR¹—, Y may behydrogen or halogen when X is —CH₂— or —NR¹, Y′ may be hydrogen orhalogen when X′ is —CH₂— or —NR¹—, R⁴, R⁵, R⁶, R⁷, R¹², R¹³, R¹⁴ and R¹⁵are each independently hydrogen, halogen, hydroxy, optionallysubstituted lower alkyl, optionally substituted lower alkoxy, optionallysubstituted lower alkenyl, optionally substituted lower alkenyloxy,optionally substituted RC(O)O wherein R is hydrogen, alkyl, alkenyl,cycloalkyl or aryl, carboxy, optionally substituted loweralkoxycarbonyl, optionally substituted lower alkenyloxycarbonyl,optionally substituted lower alkylthio, optionally substituted loweralkenylthio, optionally substituted amino, optionally substitutedcarbamoyl, guanidino, nitro, optionally substituted lower alkylsulfonyl,optionally substituted lower alkylsulfonyloxy, optionally substitutedarylsulfonyl or optionally substituted arylsulfonyloxy, excluding (i) acompound wherein Y and Y′ are simultaneously hydrogen, (ii) a compoundwherein at least one of Y and Y′ is optionally substituted RC(O), (iii)a compound wherein at least one of —X—Y and —X′—Y′ is unsubstitutedlower alkoxy, and (iv) a compound wherein —X—Y and —X′—Y′ aresimultaneously optionally substituted lower alkoxy or amino substitutedwith phenyl, salt or hydrate thereof.
 73. A pharmaceutical compositioncomprising the compound, salt or hydrate thereof according to any one ofclaims 67 to 72 and a pharmaceutically acceptable carrier.
 74. A methodfor suppressing an immune response or treating allergic diseases in apatient in need thereof, comprising administering the pharmaceuticalcomposition according to any one of claims 67 to 72 to said patient,wherein said pharmaceutical composition suppresses an immune response ortreats allergic diseases in said patient.
 75. A method for suppressingIgE production in a patient in need thereof, comprising administeringthe pharmaceutical composition according to any one of claims 67 to 72to said patient, wherein said pharmaceutical composition suppresses IgEproduction in said patient.